Is TTN p.Val28443= (c.85329T>A) pathogenic?

TTN p.Val28443= (c.85329T>A) is classified Likely benign in TTN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-08). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Val28443= (c.85329T>A)?

TTN p.Val28443= (c.85329T>A) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1G, autosomal recessive limb-girdle muscular dystrophy type 2J (ClinVar).

How common is TTN p.Val28443= (c.85329T>A) in the general population?

TTN p.Val28443= (c.85329T>A) is absent from gnomAD v4.1 (gnomAD).

TTN p.Val28443=

c.85329T>A · rs2469671651 · VCV3223314

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -4.3, phastCons 1
Overall
CADD	0.093	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TTN
Protein: p.Val28443=
Coding: c.85329T>A
MANE Select: NM_001267550
dbSNP: rs2469671651
Type: single nucleotide variant
Location: chr2:178560803 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 28443: the fibronectin type-iii 107 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

Also linked: dilated cardiomyopathy 1G autosomal recessive limb-girdle muscular dystrophy type 2J

Similar variants

TTN p.Val28443Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
TTN c.100171+1G>A Likely pathogenic ★★ same condition
TTN c.100766-1G>T Likely pathogenic ★★ same condition
TTN c.100766-2A>T Likely pathogenic ★★ same condition
TTN c.106375-2A>G Pathogenic/Likely pathogenic ★★ same condition
TTN c.106531+1G>A Pathogenic/Likely pathogenic ★★ same condition
TTN c.107224-1G>C Pathogenic/Likely pathogenic ★★ same condition
TTN c.107377+1G>A 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-val28443 (accessed [today's date]).

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