Is TTN p.Val20955fs (c.62861dup) pathogenic?

TTN p.Val20955fs (c.62861dup) is classified Pathogenic/Likely pathogenic in TTN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-06). Associated with dilated cardiomyopathy 1G.

What condition is associated with TTN p.Val20955fs (c.62861dup)?

TTN p.Val20955fs (c.62861dup) is associated with dilated cardiomyopathy 1G, autosomal recessive limb-girdle muscular dystrophy type 2J (ClinVar).

How is Familial isolated dilated cardiomyopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TTN p.Val20955fs

c.62861dup · VCV3895108

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

dilated cardiomyopathy 1G

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 304 of 363
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.023	GERP -3.3, phastCons 0.87

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

Variant & gene context

Gene: TTN
Protein: p.Val20955fs
Coding: c.62861dup
MANE Select: NM_001267550
Type: Duplication
Location: chr2:178588863 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 20955: the ig-like 112 domain

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

Disease context

dilated cardiomyopathy 1G — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2J

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

TTN p.Ala30898Ter Likely pathogenic ★★ same condition
TTN p.Arg1003fs Likely pathogenic ★★ same condition
TTN p.Arg17000Ter Pathogenic/Likely pathogenic ★★ same condition
TTN p.Arg26192fs Likely pathogenic ★★ same condition
TTN p.Arg27776fs Likely pathogenic ★★ same condition
TTN p.Asn18739delinsIleTer Likely pathogenic ★★ same condition
TTN p.Asn20321fs Likely pathogenic ★★ same condition
TTN p.Asn22211fs Pathogenic/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-val20955fs (accessed [today's date]).

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