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_000257.4(MYH7):c.3578G>A (p.Arg1193His)

CA013815

42965 (ClinVar)

Gene: MYH7
Condition: dilated cardiomyopathy
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: da44d8c5-f133-4882-8a5a-1a6c85b2e7b3
Approved on: 2025-11-13
Published on: 2025-11-13

HGVS expressions

NM_000257.4:c.3578G>A
NM_000257.4(MYH7):c.3578G>A (p.Arg1193His)
NC_000014.9:g.23419993C>T
CM000676.2:g.23419993C>T
NC_000014.8:g.23889202C>T
CM000676.1:g.23889202C>T
NC_000014.7:g.22959042C>T
NG_007884.1:g.20669G>A
ENST00000355349.4:c.3578G>A
ENST00000355349.3:c.3578G>A
NM_000257.3:c.3578G>A
More

Likely Pathogenic

Met criteria codes 4
PP3 PS4_Moderate PM2_Supporting PP1_Moderate
Not Met criteria codes 21
PS3 PS1 PS2 BA1 PP4 PP2 PM1 PM4 PM5 PM6 PVS1 BS2 BS3 BS4 BS1 BP3 BP1 BP7 BP5 BP2 BP4

Evidence Links 0

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.3578G>A (p.Arg1193His) - This variant has been reported in individuals with DCM (LMM data, OMGL data, PMIDs: 22464770, 24503780, 27532257, 29300372) 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 also segregated in 5 affected relatives with DCM from 4 families (PP1_Moderate; LMM data; OMGL data). This variant is present in gnomAD (v2.1.1), but did meet the threshold for PM2_Supporting. Computational prediction tools suggest that this variant may impact the protein (REVEL score >0.7; PP3). In summary, this variant is classified as Likely Pathogenic for DCM in an autosomal dominant manner based on PS4_Moderate, PP1_Moderate, PM2_Supporting, and PP3.
Met criteria codes
PP3
Computational prediction tools suggest that this variant may impact the protein (REVEL score >0.7; PP3).
PS4_Moderate
This variant is only reported in 9 DCM probands (2 GeneDx, 6 LMM, 1 OMGL).Also 1 LVNC (Genedx), 1 non-ischemic CM (Invitae), 1 Biventricular dilation with VT(LMM) 7/3200 LMM vs 1 in 104518 NFE in v2.1.1 7 in 3200 case genotypes vs 1 in 52259 control genotypes gives an odds ratio of 114.56 (95%CI=14.09-931.44) The lower bound 95%CI is greater than 10 (95%CI=14.09). Therefore PS4 is set to PS4_Moderate PMIDs: 22464770, 24503780, 27532257, 29300372
PM2_Supporting
This variant is present in gnomAD (v2.1.1) and did meet the threshold for PM2_Supporting.
PP1_Moderate
5 seg w DCM 4 families (4 LMM, from 3 families, 1 OMGL )
Not Met criteria codes
PS3
Functional Data is not available in the literature for this variant.
PS1
2 other variants at same codon do not meet criteria for pathogenicity
PS2
This information is not available in the literature.
BA1
Allele frequency = 0.0008% in gnomAD.
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
Not within either region of enrichment
PM4
This is a missense variant.
PM5
2 other variants at same codon do not meet criteria for pathogenicity
PM6
This information is not available in the literature.
PVS1
This is a missense variant.
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
Functional Data is not available in the literature for this variant.
BS4
Evidence for lack of segregation not reported in the literature or by ClinGen laboratories in the Internal Data Log,
BS1
Allele frequency = 0.001% in gnomAD. (europeans)
BP3
This is a missense variant.
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
This is a missense variant.
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
This information is not available in the literature.
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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