# NM_017775.4(TTC19):c.676+11del

https://sugi.bio/variant/ttc19-c-676-plus-11del

## Summary

**TTC19 c.676+11del** is classified **Likely benign** in TTC19 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-02). No gnomAD frequency available for this variant.

**At a glance:** Likely benign · review: Single submitter · rsID rs2151652386 · 1 submitter · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the TTC19 gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [TTC19](https://sugi.bio/atlas/gene/TTC19/) |
| Coding change (HGVS c.) | c.676+11del |
| MANE Select transcript | [NM_017775](https://www.ncbi.nlm.nih.gov/nuccore/NM_017775) |
| dbSNP | [rs2151652386](https://www.ncbi.nlm.nih.gov/snp/rs2151652386/) |
| Variant type | Deletion |
| Location | chr17:16006577-16006577 (GRCh38) |
| ClinVar | [VCV1567501](https://www.ncbi.nlm.nih.gov/clinvar/variation/1567501/) |

**All HGVS expressions:** `NC_000017.10:g.15909893del`, `NC_000017.11:g.16006579del`, `NG_029806.1:g.12200del`, `NM_001271420.2:c.355+11del`, `NM_017775.4:c.676+11del`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 2.953, GERP -3.81, phastCons 0.997 — highly conserved position (PP3-type support)
- Splice region: **near-intronic (+11 nt from the splice site)**.
- Non-coding constraint (Gnocchi): **Z 2.37**, o/e 0.83 (1 kb window 16,006,000–16,007,000). A higher Z means the window carries less variation than expected. Describes the 1 kb window, not this allele. No ClinGen expert panel references Gnocchi and no ACMG-calibrated threshold exists for it. *Descriptive; no cut-point applied.*
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no deletion variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency: **no gnomAD frequency available for this variant** — rarity (ACMG PM2) and BA1/BS1 cannot be assessed for this variant.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**TTC19** population constraint: LOEUF 1.049, pLI 1.5422e-09, missense-Z -0.48028. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **Leigh syndrome** — Definitive (AR)
- **mitochondrial disease** — Definitive (AR)

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 80.28, 73% of residues very-high.

## What this gene does {#gene-function}

*Describes the biological roles of TTC19 (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*


### Pathways affected {#pathways}

TTC19 participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Complex III assembly](https://reactome.org/content/detail/R-HSA-9865881) | curated |

### Molecular function & processes (GO — experimentally supported) {#go}

**Biological process:** mitochondrial respiratory chain complex III assembly.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2025-09-02.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2025-09-02 |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related TTC19 variant pages (same residue, condition, or type): [TTC19 p.Gly201fs](/variant/ttc19-p-gly201fs), [TTC19 c.832-13_832-10del](/variant/ttc19-c-832-minus-13-832-minus-10del), [TTC19 p.Lys369_Lys370insTer](/variant/ttc19-p-lys369-lys370inster), [TTC19 c.581+1_581+5del](/variant/ttc19-c-581-plus-1-581-plus-5del), [TTC19 c.677-1_680del](/variant/ttc19-c-677-minus-1-680del), [TTC19 p.Glu156fs](/variant/ttc19-p-glu156fs), [TTC19 c.312+3_312+76del](/variant/ttc19-c-312-plus-3-312-plus-76del), [TTC19 p.Ala344fs](/variant/ttc19-p-ala344fs).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 1567501). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*