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_000432.4(MYL2):c.485G>A (p.Gly162Glu)

CA010439

43479 (ClinVar)

Gene: MYL2 (HGNC:4633)

Condition: hypertrophic cardiomyopathy (MONDO:0005045)

Inheritance Mode: Autosomal dominant inheritance

UUID: 13402a8e-742a-4ab7-a80f-b053d6263f8d

Approved on: 2025-11-14

Published on: 2025-11-14

HGVS expressions

NM_000432.4(MYL2):c.485G>A (p.Gly162Glu)

NM_000432.4:c.485G>A

NC_000012.12:g.110911093C>T

CM000674.2:g.110911093C>T

NC_000012.11:g.111348897C>T

CM000674.1:g.111348897C>T

NC_000012.10:g.109833280C>T

NG_007554.1:g.14485G>A

ENST00000228841.15:c.485G>A

ENST00000663220.1:c.428G>A

ENST00000228841.12:c.485G>A

ENST00000548438.1:c.443G>A

NM_000432.3:c.485G>A

Likely Pathogenic

PP1_Strong PM2_Supporting PS4_Supporting PP3

BS3 BS1 BP4 PM6 PM5 PS2 PS3 PS1 BA1

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 MYL2 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Cardiomyopathy VCEP

NM_000432.4(MYL2):c.485G>A (p.Gly162Glu). This variant has been identified in individuals with HCM and other cardiomyopathies (ClinVar Variation ID 164114) and segregated with disease in 11 affected relatives from one family (PP1_Strong; Renaudin 2018 PMID: 29549657). It was absent from large population studies (PM2_Supporting; https://gnomad.broadinstitute.org/; v.2.1). The variant is statistically increased in individuals with HCM compared to controls (OR lower 95% CI>5), therefore, the PS4 criterion has been applied at supporting strength (PS4_Supporting). Computational prediction tools and conservation analyses suggest that this variant may impact the protein (PP3; REVEL score ≥0.70). In summary, this variant meets criteria to be classified as likely pathogenic for hypertrophic cardiomyopathy in an autosomal dominant manner based on PS4_Supporting, PM2_Supporting, PP1_Strong, PP3.

PP1_Strong

Renaudin - 1 HCM and 11 segregations

PM2_Supporting

Absent from gnomAD 2.1 and 4.1.0

PS4_Supporting

Walsh 2017 - 3/2650 LMM Gnomad 2.1 - absent (NFE denominator as variant in same codon 112196) 3 in 2650 case genotypes vs 1 in 56098 control genotypes gives an odds ratio of 63.58 (95%CI=6.61-611.41) Lower bound CI: Strong 95%CI=6.61 (threshold for strong ≥20) Moderate 95%CI=6.61 (threshold for moderate ≥10) Supporting 95%CI=6.61 (threshold for supporting ≥5) The lower bound 95%CI is greater than 5 (95%CI=6.61). Therefore PS4 is set to PS4_Supporting

PP3

Computational prediction tools and conservation analyses suggest that this variant may impact the protein (PP3; REVEL score ≥0.70)

BS3

no studies

BS1