Is TTN p.Val3355fs (c.10062del) pathogenic?

TTN p.Val3355fs (c.10062del) is classified Likely pathogenic in TTN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-17). Absent from gnomAD; Associated with autosomal recessive limb-girdle muscular dystrophy type 2J.

How common is TTN p.Val3355fs (c.10062del) in the general population?

TTN p.Val3355fs (c.10062del) is absent from gnomAD (gnomAD).

How is Titin-related limb-girdle muscular dystrophy R10 inherited?

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

TTN p.Val3355fs

Q: What condition is associated with TTN p.Val3355fs (c.10062del)?

TTN p.Val3355fs (c.10062del) is associated with autosomal recessive limb-girdle muscular dystrophy type 2J, dilated cardiomyopathy 1G (ClinVar).

c.10062del · rs1553983844 · VCV534999

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2J

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 43 of 363
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.86	GERP 0.95, phastCons 0.28

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TTN
Protein: p.Val3355fs
Coding: c.10062del
MANE Select: NM_001267550
dbSNP: rs1553983844
Type: Deletion
Location: chr2:178764229 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 3355: the ig-like 20 domain

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

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2J — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy 1G

For Titin-related limb-girdle muscular dystrophy R10 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

TTN p.Val3355= Likely benign ★ same residue
TTN c.32888-1del Likely pathogenic ★★ same condition
TTN c.49648+2del Pathogenic ★★ same condition
TTN c.80003_80028+4del Likely pathogenic ★★ same condition
TTN c.86822-1del Likely pathogenic ★★ same condition
TTN p.Ala14213fs Likely pathogenic ★★ same condition
TTN p.Ala18013fs Likely pathogenic ★★ same condition
TTN p.Ala18143fs 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-val3355fs (accessed [today's date]).

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