Is TTN p.Ile19081= (c.57243T>A) pathogenic?

TTN p.Ile19081= (c.57243T>A) is classified Conflicting classifications of pathogenicity in TTN (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-12). Very rare (popmax 0.00593%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Ile19081= (c.57243T>A)?

TTN p.Ile19081= (c.57243T>A) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1G, autosomal recessive limb-girdle muscular dystrophy type 2J (ClinVar).

How common is TTN p.Ile19081= (c.57243T>A) in the general population?

TTN p.Ile19081= (c.57243T>A) is very rare (popmax 0.00593%, nfe) (gnomAD).

TTN p.Ile19081=

c.57243T>A · rs1185555417 · VCV597207

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00593%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.3	GERP 1.8, phastCons 1
Overall
CADD	1.221	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00593% European (non-Finnish) · 70/1,179,574 alleles

Filtering AF 0.00478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00439%

Overall 0.0044% 71/1,613,168 alleles · very rare exomes 69/1,461,078 · genomes 2/152,090 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00593%	16,851
Remaining individualsnot grpmax-eligible	0.0016%	62,440

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TTN
Protein: p.Ile19081=
Coding: c.57243T>A
MANE Select: NM_001267550
dbSNP: rs1185555417
Type: single nucleotide variant
Location: chr2:178597927 (GRCh38)

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

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-ile19081 (accessed [today's date]).

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