Is TTN p.Ala3955fs (c.11861dup) pathogenic?

TTN p.Ala3955fs (c.11861dup) is classified Likely pathogenic in TTN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-04). Associated with muscular dystrophy.

What condition is associated with TTN p.Ala3955fs (c.11861dup)?

TTN p.Ala3955fs (c.11861dup) is associated with muscular dystrophy (ClinVar).

TTN p.Ala3955fs

c.11861dup · VCV3384049

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

muscular dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 48 of 363
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.29	GERP -5.7, phastCons 0.37

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: TTN
Protein: p.Ala3955fs
Coding: c.11861dup
MANE Select: NM_001267550
Type: Duplication
Location: chr2:178741371 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)

Full TTN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TTN p.Ser20712fs Likely pathogenic ★★ same condition
TTN p.Ala3955= Likely benign ★ same residue
TTN p.Gln35879Ter Pathogenic/Likely pathogenic ★★ same condition
TTN p.Glu34454fs Pathogenic/Likely pathogenic ★★ same condition
TTN c.1800+1G>A Conflicting classifications of pathogenicity ★ same condition
TTN p.Lys3815Thr Uncertain significance ★ ⚠ same condition
TTN p.Ile34024del Uncertain significance same condition
TTN p.Ala30898Ter Likely pathogenic ★★ same type

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-ala3955fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown