Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001276345.2(TNNT2):c.508GAG[3] (p.Glu173del)

CA004651

43648 (ClinVar)

Gene: TNNT2 (HGNC:7139)

Condition: hypertrophic cardiomyopathy (MONDO:0005045)

Inheritance Mode: Autosomal dominant inheritance

UUID: d3f3f93b-d3df-4db4-a82f-ef5711de2db4

Approved on: 2025-11-13

Published on: 2025-11-13

HGVS expressions

NM_001276345.2:c.517_519del

NM_001276345.2(TNNT2):c.508GAG[3] (p.Glu173del)

NM_001276345.2:c.508GAG[3]

NC_000001.11:g.201363386_201363388del

CM000663.2:g.201363386_201363388del

NC_000001.10:g.201332514_201332516del

CM000663.1:g.201332514_201332516del

NC_000001.9:g.199599137_199599139del

NG_007556.1:g.19299_19301del

ENST00000455702.7:c.502_504del

ENST00000367318.10:c.487_489del

ENST00000367322.6:c.484_486del

ENST00000412633.3:c.487_489del

ENST00000422165.6:c.517_519del

ENST00000438742.6:c.469_471del

ENST00000455702.6:c.502_504del

ENST00000651504.1:n.981_983del

ENST00000656932.1:c.517_519del

ENST00000658476.1:c.487_489del

ENST00000660295.1:c.487_489del

ENST00000662159.1:c.163-1380_163-1378del

ENST00000663843.1:c.*417_*419del

ENST00000666449.1:c.487_489del

ENST00000236918.11:c.517_519del

ENST00000360372.8:c.397_399del

ENST00000367315.6:c.493_495del

ENST00000367317.8:c.472_474del

ENST00000367318.9:c.487_489del

ENST00000367320.6:c.397_399del

ENST00000367322.5:c.487_489del

ENST00000421663.6:c.310_312del

ENST00000438742.5:c.472_474del

ENST00000455702.5:c.517_519del

ENST00000458432.6:c.310_312del

ENST00000460780.5:n.810_812del

ENST00000466570.5:n.743_745del

ENST00000491504.5:n.1726_1728del

ENST00000509001.5:c.487_489del

ENST00000515042.5:n.413_415del

NM_000364.3:c.517_519del

NM_001001430.2:c.487_489del

NM_001001431.2:c.487_489del

NM_001001432.2:c.472_474del

NM_001276345.1:c.517_519del

NM_001276346.1:c.397_399del

NM_001276347.1:c.487_489del

NM_000364.4:c.517_519del

NM_001001430.3:c.487_489del

NM_001001431.3:c.487_489del

NM_001001432.3:c.472_474del

NM_001276346.2:c.397_399del

NM_001276347.2:c.487_489del

Pathogenic

PM6_Supporting PP1_Strong PM4 PS4_Moderate PM2_Supporting PS3_Supporting

PS2 BA1 BS3 BS1

Evidence Links 0

Expert Panel

Cardiomyopathy VCEP

Criteria Specification Information

Criteria Specification: ClinGen Cardiomyopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for TNNT2 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

NM_001276345.2(TNNT2):c.517_519del (p.Glu173del) - This variant has been reported in individuals with HCM and other cardiomyopathies (LMM data, PMIDs: 7898523, 11606294, 12707239, 20624503, 22144547, 22260945, 24792744, 27532257, 27662471, 28771489) and is statistically increased in individuals with cardiomyopathy compared to controls [OR lower 95% CI >10]. Therefore, the PS4_Moderate criterion has been applied. This variant is absent from gnomAD v2.1.1 (PM2_Supporting; http://gnomad.broadinstitute.org). This variant segregated with disease in multiple affected individuals across multiple families (PP1_Strong; OMGL Data, LMM Data, PMID: 7898523). This variant has been confirmed as de novo (PM6_Supporting; OMGL Data). Functional studies have been reported and are sufficient to apply PS3_Supporting (PMID: 10497196, 10731693, 14636924, 22579624, 24480310, 27036851). This variant is a deletion 1 amino acid and is not predicted to alter the protein reading-frame (PM4). In summary, this variant has been classified as Pathogenic for HCM in an autosomal dominant manner based on PS4_Moderate, PM2_Supporting, PP1_Strong, PM6_Supporting, PS3_Supporting, and PM4.

PM6_Supporting

This variant has been confirmed as a de novo occurrences (PM6_Supporting; OMGL Data).

PP1_Strong

This variant segregated with disease in multiple affected individuals across multiple families (PP1_Strong; OMGL Data, LMM Data, PMID: 7898523).

PM4

This variant is a deletion 1 amino acid and is not predicted to alter the protein reading-frame (PM4).

PS4_Moderate

This variant has been reported in individuals with HCM (LMM data, PMIDs: 7898523, 11606294, 12707239, 20624503, 22144547, 22260945, 24792744, 27532257, 27662471, 28771489) and is statistically increased in individuals with cardiomyopathy compared to controls [OR lower 95% CI >10]. Therefore, PS4_Moderate criteria has been applied.

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting; http://gnomad.broadinstitute.org).

PS3_Supporting

Functional studies have been reported and are sufficient to apply PS3_Supporting (PMID: 10497196, 10731693, 14636924, 22579624, 24480310, 27036851).

PS2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BA1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS3

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.