Is TNNT2 p.Arg78= (c.234G>A) pathogenic?

TNNT2 p.Arg78= (c.234G>A) is classified Uncertain significance in TNNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-15). Absent from gnomAD v4.1; Associated with cardiomyopathy, familial restrictive, 3.

What condition is associated with TNNT2 p.Arg78= (c.234G>A)?

TNNT2 p.Arg78= (c.234G>A) is associated with cardiomyopathy, familial restrictive, 3, hypertrophic cardiomyopathy 2, dilated cardiomyopathy 1D (ClinVar).

How common is TNNT2 p.Arg78= (c.234G>A) in the general population?

TNNT2 p.Arg78= (c.234G>A) is absent from gnomAD v4.1 (gnomAD).

TNNT2 p.Arg78=

c.234G>A · rs2527027718 · VCV2413929

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cardiomyopathy, familial restrictive, 3

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 0.98	GERP 0.89, phastCons 1
Overall
CADD	14.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TNNT2
Protein: p.Arg78=
Coding: c.234G>A
MANE Select: NM_001276345
dbSNP: rs2527027718
Type: single nucleotide variant
Location: chr1:201365670 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.93 · 25 PDB
Residue 78: the 'disordered' region

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

Disease context

cardiomyopathy, familial restrictive, 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hypertrophic cardiomyopathy 2 dilated cardiomyopathy 1D

Similar variants

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
TNNT2 p.Arg102Gln 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-arg78 (accessed [today's date]).

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