Is TNNT2 p.Val7= (c.21G>T) pathogenic?

TNNT2 p.Val7= (c.21G>T) is classified Likely benign in TNNT2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-06-20). Very rare (popmax 0.004%, afr); Associated with dilated cardiomyopathy 1D.

What condition is associated with TNNT2 p.Val7= (c.21G>T)?

TNNT2 p.Val7= (c.21G>T) is associated with dilated cardiomyopathy 1D, hypertrophic cardiomyopathy 2, cardiomyopathy, familial restrictive, 3 (ClinVar).

How common is TNNT2 p.Val7= (c.21G>T) in the general population?

TNNT2 p.Val7= (c.21G>T) is very rare (popmax 0.004%, afr) (gnomAD).

How is Left ventricular noncompaction inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TNNT2 p.Val7=

c.21G>T · rs777128825 · VCV517982

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

dilated cardiomyopathy 1D

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.8	GERP -4.1
Overall
CADD	5.527	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,922 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,614,036 alleles · very rare exomes 3/1,461,850 · genomes 1/152,186 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,974
European (non-Finnish)	8.47e-05%	1,180,012

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: TNNT2
Protein: p.Val7=
Coding: c.21G>T
MANE Select: NM_001276345
dbSNP: rs777128825
Type: single nucleotide variant
Location: chr1:201373234 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.93 · 25 PDB
Residue 7: the 'disordered' region

Full TNNT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dilated cardiomyopathy 1D — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy 2 cardiomyopathy, familial restrictive, 3

For Left ventricular noncompaction (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages

Similar variants

TNNT2 p.Val7Ala Uncertain significance ★ ⚠ same residue
TNNT2 c.851+1G>A Likely pathogenic ★★★ same condition
TNNT2 p.Arg104His Likely pathogenic ★★★ same condition
TNNT2 p.Trp297Ter Likely pathogenic ★★★ same condition
TNNT2 p.Arg296Cys Uncertain significance ★★★ ⚠ same condition
TNNT2 p.Arg288Cys Likely benign ★★★ same condition
TNNT2 c.851+1G>C Pathogenic/Likely pathogenic ★★ same condition
TNNT2 c.851+1G>T 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/tnnt2-p-val7 (accessed [today's date]).

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