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]
  • See Evidence submitted by expert panel for details.

Variant: NM_000257.4(MYH7):c.1141G>A (p.Ala381Thr)

CA010273

179272 (ClinVar)

Gene: MYH7
Condition: hypertrophic cardiomyopathy
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: e0d64c3c-f0aa-4f9f-bc63-0e06e24e6c80
Approved on: 2021-09-22
Published on: 2021-10-01

HGVS expressions

NM_000257.4:c.1141G>A
NM_000257.4(MYH7):c.1141G>A (p.Ala381Thr)
NC_000014.9:g.23429345C>T
CM000676.2:g.23429345C>T
NC_000014.8:g.23898554C>T
CM000676.1:g.23898554C>T
NC_000014.7:g.22968394C>T
NG_007884.1:g.11317G>A
ENST00000355349.4:c.1141G>A
ENST00000355349.3:c.1141G>A
NM_000257.3:c.1141G>A
More

Uncertain Significance

Met criteria codes 2
PM2 PM1
Not Met criteria codes 19
BP3 BP7 BP4 PS3 PS2 PS4 PS1 PP1 PP3 PP4 PM4 PM6 PVS1 PM5_Supporting BA1 BS2 BS3 BS4 BS1

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.1141G>A (p.Ala381Thr) variant has been identified in 1 neonate with HCM and repolarization abnormalities (LMM pers. comm.); however this case data is insufficient to apply PS4. This variant was absent from large population studies (PM2; gnomAD v2.1.1, http://gnomad.broadinstitute.org). This variant lies in the head region of the protein (aa 181-937) and missense variants in this region are statistically more likely to be associated with HCM (PM1; Walsh 2017 PMID:27532257). Computational prediction tools and conservation analysis were mixed about the potential impact of this variant. In summary, due to insufficient evidence, this variant is classified as uncertain significance for hypertrophic cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): PM2, PM1.
Met criteria codes
PM2
Absent from gnomAD with sufficient coverage
PM1
Missense variant in residue 181-937
Not Met criteria codes
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
LMM is only case reported. No literature in HGMD, Google Scholar, or ClinVar. This variant has been reported in 1 neonate with HCM and depolarization abnormalities (LMM pers. comm.); however this case data is insufficient to apply PS4.
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
Computational tools are mixed
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5_Supporting
Walsh et al 2017, PMID 27532257: Found in p.A381D in 5/382 patients and classified as LP. But, A>D more severe change than A>T. Not enough other evidence to warrant full classification.
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
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
BS4
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.
¤ Powered by BCM's Genboree.