Is TTN p.Pro23243= (c.69729A>T) pathogenic?

TTN p.Pro23243= (c.69729A>T) is classified Likely benign in TTN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-25). Very rare (popmax 0.000944%, nfe); Associated with dilated cardiomyopathy 1G.

What condition is associated with TTN p.Pro23243= (c.69729A>T)?

TTN p.Pro23243= (c.69729A>T) is associated with dilated cardiomyopathy 1G, autosomal recessive limb-girdle muscular dystrophy type 2J (ClinVar).

How common is TTN p.Pro23243= (c.69729A>T) in the general population?

TTN p.Pro23243= (c.69729A>T) is very rare (popmax 0.000944%, nfe) (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.Pro23243=

c.69729A>T · rs2468725433 · VCV2935405

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000944%, nfe)

Conditions

dilated cardiomyopathy 1G

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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 1.3	GERP -2.1, phastCons 1
Overall
CADD	0.542	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000944% European (non-Finnish) · 11/1,164,668 alleles

Filtering AF 0.000507% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00037%

Overall 0.000701% 11/1,568,950 alleles · very rare exomes 11/1,416,756 · genomes 0/152,194 · joint denominator

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.Pro23243=
Coding: c.69729A>T
MANE Select: NM_001267550
dbSNP: rs2468725433
Type: single nucleotide variant
Location: chr2:178576403 (GRCh38)

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)

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-pro23243 (accessed [today's date]).

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