Is TTN p.Asp18299fs (c.54894del) pathogenic?

TTN p.Asp18299fs (c.54894del) is classified Likely pathogenic in TTN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-09). Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Asp18299fs (c.54894del)?

TTN p.Asp18299fs (c.54894del) is associated with Cardiovascular phenotype (ClinVar).

TTN p.Asp18299fs

c.54894del · VCV4193718

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Cardiovascular phenotype

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 283 of 363
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 2.9, phastCons 1

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

Variant & gene context

Gene: TTN
Protein: p.Asp18299fs
Coding: c.54894del
MANE Select: NM_001267550
Type: Deletion
Location: chr2:178602508 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 18299: the fibronectin type-iii 32 domain

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TTN c.80003_80028+4del Likely pathogenic ★★ same condition
TTN p.Ala18143fs Likely pathogenic ★★ same condition
TTN p.Ala24870fs Pathogenic/Likely pathogenic ★★ same condition
TTN p.Ala29119fs Pathogenic/Likely pathogenic ★★ same condition
TTN p.Arg13741fs Likely pathogenic ★★ same condition
TTN p.Arg14079fs Likely pathogenic ★★ same condition
TTN p.Arg27948fs Likely pathogenic ★★ same condition
TTN p.Arg28796fs 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-asp18299fs (accessed [today's date]).

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