Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000257.3(MYH7):c.2360G>A (p.Arg787His)

CA012239

42900 (ClinVar)

Gene: MYH7
Condition: hypertrophic cardiomyopathy
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: de961e5a-a5f1-47f5-abee-524b09b41cc0
Approved on: 2025-11-14
Published on: 2025-11-14

HGVS expressions

NM_000257.3:c.2360G>A
NM_000257.3(MYH7):c.2360G>A (p.Arg787His)
NC_000014.9:g.23425345C>T
CM000676.2:g.23425345C>T
NC_000014.8:g.23894554C>T
CM000676.1:g.23894554C>T
NC_000014.7:g.22964394C>T
NG_007884.1:g.15317G>A
ENST00000355349.4:c.2360G>A
ENST00000355349.3:c.2360G>A
NM_000257.4:c.2360G>A
More

Benign

Met criteria codes 4
BS4 BP2 BA1 PM1
Not Met criteria codes 9
BS3 BS1 BP4 PS3 PM5 PM2 PS4 PP1 PP3

Evidence Links 3

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Cardiomyopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MYH7 Version 2.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cardiomyopathy VCEP
NM_000257.4(MYH7):c.2360G>A (p.Arg787His).This variant has been identified in 0.2% (FAF 95% CI; 200/91078) of South Asian chromosomes, including 1 homozygote, in gnomAD v4.1.0 (BA1; https://gnomad.broadinstitute.org). Additionally, this variant has been identified in multiple affected individuals with other pathogenic variants (BP2; summarized in ClinVar ID: 42900) and was shown not to segregate with disease in 2 affected individuals from 2 families (BS4; Oxford Medical Genetics Laboratory (OMGL)). This variant lies in a region of the protein where variants are statistically more likely to be disease-associated (PM1_Strength; Walsh 2019 PMID: 30696458). This is not considered to be in conflict with BA1 since benign variation within this region was considered during that analysis. In summary, this variant meets criteria to be is classified as benign for hypertrophic cardiomyopathy in an autosomal dominant manner based on BA1, BP2, BS4 and PM1.
Met criteria codes
BS4
Additionally, this variant was shown not to segregate with disease in 2 affected individuals from 2 families (BS4; Oxford Medical Genetics Laboratory (OMGL)). Individual 1: A likely pathogenic variant in MYBPC3 has been identified in this family following non-segregation in some of the affected relatives. MYH7 variant does not segregate. Individual 2. Also Homozygous for the Likely path MYBPC3 variant. Affected brother also has MYBPC3 variant but not MYH7 variant.
BP2
Variant identified in multiple affected individuals with other pathogenic variants (including ClinVar 42900 and SHaRe data)
Variant identified in 2 probands with HCM - however both carry pathogenic variants in other genes PubMed:21959974
BA1
This variant has been identified in 0.2% (FAF 95% CI; 200/91078) of South Asian chromosomes, including 1 homozygote, in gnomAD v4.1.0 (BA1; https://gnomad.broadinstitute.org).
PM1
This variant lies in a region of the protein where variants are statistically more likely to be disease-associated (PM1_Strength; Walsh 2019 PMID: 30696458). This is not considered to be in conflict with BA1 since benign variation within this region was considered during that analysis.
Variants in head region of the protein (aa 181-937) are statistically more likely to be disease-associated PubMed:27532257
This variant lies in a region of the protein where variants are statistically more likely to be disease-associated (PM1_Strength; Walsh 2019 PMID: 30696458). PubMed:30696458
Not Met criteria codes
BS3
no studies
BS1
This variant has been identified in 0.2% (FAF 95% CI; 200/91078) of South Asian chromosomes, including 1 homozygote, in gnomAD v4.1.0 (BA1; https://gnomad.broadinstitute.org).
BP4
Comp and cons conflicting, revel score not low enough
PS3
no studies
PM5
2 VUS, one multiple submitter, 1 single submitter
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
PM2 not met
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
Comp and cons conflicting, revel score not low enough
Curation History
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