Is TTN p.Phe14331fs (c.42993del) pathogenic?

TTN p.Phe14331fs (c.42993del) is classified Likely pathogenic in TTN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-18). Ultra-rare (gnomAD MAF 2.482e-06); Associated with dilated cardiomyopathy 1G.

What condition is associated with TTN p.Phe14331fs (c.42993del)?

TTN p.Phe14331fs (c.42993del) is associated with dilated cardiomyopathy 1G, autosomal recessive limb-girdle muscular dystrophy type 2J (ClinVar).

How common is TTN p.Phe14331fs (c.42993del) in the general population?

TTN p.Phe14331fs (c.42993del) is ultra-rare (gnomAD MAF 2.482e-06) (gnomAD).

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.Phe14331fs

c.42993del · rs2471501034 · VCV2948366

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 2.482e-06)

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 233 of 363
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1

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

Population frequency

dbSNP / gnomAD

Global frequency 0.000248% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: TTN
Protein: p.Phe14331fs
Coding: c.42993del
MANE Select: NM_001267550
dbSNP: rs2471501034
Type: Deletion
Location: chr2:178633280 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 14331: a β-strand

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 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
TTN p.Ala19403fs 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-phe14331fs (accessed [today's date]).

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