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 related information was provided by the message!
  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_000257.4(MYH7):c.3578G>A (p.Arg1193His)

CA013815

42965 (ClinVar)

Gene: MYH7
Condition: hypertrophic cardiomyopathy
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: da44d8c5-f133-4882-8a5a-1a6c85b2e7b3
Approved on: 2021-12-22
Published on: 2021-12-22

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 PM2 PP1_Moderate PS4_Moderate
Not Met criteria codes 21
BA1 PP2 PP4 PM5 PM6 PM1 PM4 BS2 BS1 BS4 BS3 PS3 PS1 PS2 BP3 BP1 PVS1 BP4 BP7 BP2 BP5

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cardiomyopathy VCEP
The NM_000257.4(MYH7):c.3578G>A (p.Arg1193His) variant has been identified in at least 9 individuals with DCM, including 1 individual with an additional variant in another gene that may contribute to their disease and 1 individual with DCM and a bicuspid aortic valve (PS4_Moderate; GeneDx pers. comm.; LMM pers. comm.; OMGL pers. comm.). This variant also segregated in 5 affected relatives with DCM from 4 families (PP1_Moderate; LMM pers. comm.; OMGL pers. comm.). Additionally, this variant has also been reported in 1 individual with LVNC, 1 individual with non-ischemic cardiomyopathy and 1 individual with biventricular dilation with ventricular tachycardia (GeneDx pers. comm., Invitae pers. comm., LMM pers. comm.). This variant was absent from large population studies (PM2; gnomAD v2.1.1, http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may impact the protein (PP3). In summary, this variant meets criteria to be classified as likely pathogenic for dilated cardiomyopathy in an autosomal dominant manner. ACMG/AMP Criteria applied: PS4_Moderate, PP1_Moderate, PM2, PP3.
Met criteria codes
PP3
In silico analysis programs (SIFT, PolyPhen-2, Mutation Taster) predict this variant to have an impact on the protein function
PM2
Allele frequency = 0.001% in gnomAD. (europeans)
PP1_Moderate
5 seg w DCM 4 families (4 LMM, from 3 families, 1 OMGL )
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)
Not Met criteria codes
BA1
Allele frequency = 0.0008% in gnomAD.
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
2 other variants at same codon do not meet criteria for pathogenicity
PM6
This information is not available in the literature.
PM1
not in head domain
PM4
This is a missense variant.
BS2
This information is not available in the literature or population databases.
BS1
Allele frequency = 0.001% in gnomAD. (europeans)
BS4
Evidence for lack of segregation not reported in the literature or by ClinGen laboratories in the Internal Data Log,
BS3
Functional Data is not available in the literature for this variant.
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.
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
PVS1
This is a missense variant.
BP4
In silico analysis programs (SIFT, PolyPhen-2, Mutation Taster) predict this variant to have an impact on the protein function
BP7
This is a missense variant.
BP2
This information is not available in the literature.
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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