Is TTN p.Ser8065= (c.24195C>T) pathogenic?

TTN p.Ser8065= (c.24195C>T) is classified Benign/Likely benign in TTN (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-01-31). Rare (popmax 0.468%, afr); Associated with dilated cardiomyopathy 1G.

What condition is associated with TTN p.Ser8065= (c.24195C>T)?

TTN p.Ser8065= (c.24195C>T) is associated with dilated cardiomyopathy 1G, cardiomyopathy, tibial muscular dystrophy (ClinVar).

How common is TTN p.Ser8065= (c.24195C>T) in the general population?

TTN p.Ser8065= (c.24195C>T) is rare (popmax 0.468%, afr) (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.Ser8065=

c.24195C>T · rs182425565 · VCV46727

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

gnomAD v4.1

Rare

rare (popmax 0.468%, afr)

Conditions

dilated cardiomyopathy 1G

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 -1.2	GERP -5.6
Overall
CADD	2.884	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.468% African / African-American · 351/75,006 alleles

Filtering AF 0.428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.412%

Overall 0.0242% 391/1,613,614 alleles · rare exomes 204/1,461,408 · genomes 187/152,206 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.468%	214
Remaining individualsnot grpmax-eligible	0.0336%	2,975
Admixed American	0.0267%	3,750
European (non-Finnish)	0.000254%	393,218

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.Ser8065=
Coding: c.24195C>T
MANE Select: NM_001267550
dbSNP: rs182425565
Type: single nucleotide variant
Location: chr2:178719195 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 8065: the ig-like 63 domain; 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: cardiomyopathy tibial muscular dystrophy myopathy, myofibrillar, 9, with early respiratory failure autosomal recessive limb-girdle muscular dystrophy type 2J early-onset myopathy with fatal cardiomyopathy

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 p.Ser8065Cys Uncertain significance ★ same residue
TTN p.Ser8065Pro Likely benign ★ ⚠ 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

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-ser8065 (accessed [today's date]).

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