Is TNNT2 p.Ile150= (c.450C>T) pathogenic?

TNNT2 p.Ile150= (c.450C>T) is classified Likely benign in TNNT2 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2025-12-07). Very rare (popmax 0.00525%, nfe); Associated with cardiomyopathy.

What condition is associated with TNNT2 p.Ile150= (c.450C>T)?

TNNT2 p.Ile150= (c.450C>T) is associated with cardiomyopathy, hypertrophic cardiomyopathy 2, dilated cardiomyopathy 1D (ClinVar).

How common is TNNT2 p.Ile150= (c.450C>T) in the general population?

TNNT2 p.Ile150= (c.450C>T) is very rare (popmax 0.00525%, nfe) (gnomAD).

TNNT2 p.Ile150=

c.450C>T · rs200604266 · VCV516901

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00525%, nfe)

Conditions

cardiomyopathy

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 2.3	GERP -3, phastCons 1
Overall
CADD	7.751	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00525% European (non-Finnish) · 62/1,179,986 alleles

Filtering AF 0.00418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00409% 66/1,613,306 alleles · very rare exomes 64/1,460,974 · genomes 2/152,332 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00525%	19,032
Admixed American	0.00333%	30,012
Remaining individualsnot grpmax-eligible	0.0016%	62,490
African / African-American	0.00133%	75,056

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.Ile150=
Coding: c.450C>T
MANE Select: NM_001276345
dbSNP: rs200604266
Type: single nucleotide variant
Location: chr1:201364337 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.93 · 25 PDB
Residue 150: the 'disordered' region

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

Disease context

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

Also linked: hypertrophic cardiomyopathy 2 dilated cardiomyopathy 1D cardiomyopathy, familial restrictive, 3

Similar variants

TNNT2 p.Ile150Val Uncertain significance ★★ ⚠ same residue
TNNT2 p.Ile150Asn Uncertain significance ★ ⚠ same residue
TNNT2 p.Ile150Leu 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

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-ile150 (accessed [today's date]).

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