TTN p.Glu645del
c.1933_1935del · rs774138200 · VCV426953
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0217%, amr)
Conditions
1
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 6.2 | GERP 2.3, phastCons 1 |
| Overall | ||
| CADD | 17.79 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0217%
Admixed American · 13/59,982 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.000806%
13/1,612,778 alleles · ultra-rare
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- TTN
- Protein
- p.Glu645del
- Coding
- c.1933_1935del
- MANE Select
- NM_001267550
- dbSNP
- rs774138200
- Type
- Deletion
- Location
- chr2:178789981 (GRCh38)
- Gene constraint
- LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Similar variants
- TTN p.Glu645= Likely benign ★★ same residue
- TTN c.80003_80028+4del Likely pathogenic ★★ same condition
- TTN p.Ala18143fs Likely pathogenic ★★ same condition
- TTN p.Ala24870fs Pathogenic/Likely pathogenic ★★ same condition
- TTN p.Ala29119fs Pathogenic/Likely pathogenic ★★ same condition
- TTN p.Arg13741fs Likely pathogenic ★★ same condition
- TTN p.Arg14079fs Likely pathogenic ★★ same condition
- TTN p.Arg27948fs Likely pathogenic ★★ same condition
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ttn-p-glu645del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown