TTN p.Trp14174Ter
c.42521G>A · VCV3341104
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
congenital myopathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 231 of 363 |
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2.8, phastCons 1 |
| Overall | ||
| CADD | 54.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- TTN
- Protein
- p.Trp14174Ter
- Coding
- c.42521G>A
- MANE Select
- NM_001267550
- Type
- single nucleotide variant
- Location
- chr2:178633978 (GRCh38)
- Gene constraint
- LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
- Residue 14174
- the fibronectin type-iii 2 domain
Similar variants
- TTN p.Pro32799Thr Uncertain significance ★★ ⚠ same condition
- TTN p.Ser21179Gly Uncertain significance ★★ ⚠ same condition
- TTN c.19427-8T>G Uncertain significance ★ same condition
- TTN p.Ala7474Thr Conflicting classifications of pathogenicity ★ same condition
- TTN p.Arg14967Ter Conflicting classifications of pathogenicity ★ same condition
- TTN p.Glu12116Gly Conflicting classifications of pathogenicity ★ same condition
- TTN p.Ile11559Val Conflicting classifications of pathogenicity ★ ⚠ same condition
- TTN p.Phe10097Ser Uncertain significance ★ ⚠ 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-trp14174ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown