Is TTN p.Ser2973= (c.8919C>G) pathogenic?

TTN p.Ser2973= (c.8919C>G) is classified Benign in TTN (ClinVar, Multiple submitters, 17 submitters; last evaluated 2026-02-04). Common (popmax 17%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Ser2973= (c.8919C>G)?

TTN p.Ser2973= (c.8919C>G) is associated with Cardiovascular phenotype, tibial muscular dystrophy, myopathy, myofibrillar, 9, with early respiratory failure (ClinVar).

TTN p.Ser2973=

Q: How common is TTN p.Ser2973= (c.8919C>G) in the general population?

TTN p.Ser2973= (c.8919C>G) is common (popmax 17%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.8919C>G · rs4894045 · VCV47571

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 17 submitters

gnomAD v4.1

Common

common (popmax 17%, amr) — too common for a highly-penetrant pathogenic allele

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 3	GERP 0.01, phastCons 1
Overall
CADD	7.954	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17% Admixed American · 10,221/59,978 alleles

Filtering AF 16.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.7%

Overall 4% 64,543/1,613,666 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	17%	6
South Asian	16.2%	6
African / African-American	6.92%	14
Finnishnot grpmax-eligible	5.65%	18
Middle Eastern	4.61%	22
Remaining individualsnot grpmax-eligible	4.27%	23
Ashkenazi Jewishnot grpmax-eligible	2.77%	36
European (non-Finnish)	2.24%	45
East Asian	1.35%	74

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.Ser2973=
Coding: c.8919C>G
MANE Select: NM_001267550
dbSNP: rs4894045
Type: single nucleotide variant
Location: chr2:178768917 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 2973: the ig-like 17 domain; a β-strand

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: tibial muscular dystrophy myopathy, myofibrillar, 9, with early respiratory failure dilated cardiomyopathy 1G autosomal recessive limb-girdle muscular dystrophy type 2J early-onset myopathy with fatal cardiomyopathy

Similar variants

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
TTN c.107377+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-ser2973 (accessed [today's date]).

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