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]
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  • See Evidence submitted by expert panel for details.

Variant: NM_000257.4(MYH7):c.2714G>C (p.Cys905Ser)

CA012920

181203 (ClinVar)

Gene: MYH7
Condition: hypertrophic cardiomyopathy
Link to MONDO
UUID: f4440cf7-6088-4eaf-b8ee-437aced70a42

HGVS expressions

NM_000257.4:c.2714G>C
NM_000257.4(MYH7):c.2714G>C (p.Cys905Ser)
ENST00000355349.4:c.2714G>C
ENST00000355349.3:c.2714G>C
NM_000257.3:c.2714G>C
NC_000014.9:g.23424115C>G
CM000676.2:g.23424115C>G
NC_000014.8:g.23893324C>G
CM000676.1:g.23893324C>G
NC_000014.7:g.22963164C>G
NG_007884.1:g.16547G>C

Uncertain Significance

Met criteria codes 3
PM1 PM2 PP3
Not Met criteria codes 17
PM4 PM6 PS3 PM5 PS2 PS4 PS1 BA1 PVS1 BP7 BP5 BP2 BP4 BS4 BS3 BS1 PP1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cardiomyopathy VCEP
The NM_000257.4: c.2714G>C (p.Cys905Ser) variant in MYH7 has been reported in 1 individual with HCM (GeneDx pers. comm.); however this data is insufficient to apply the PS4 criterion. This variant was absent from large population studies (PM2; http://gnomad.broadinstitute.org, v2.1.1). 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 suggest that this variant may impact the protein (PP3). 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, PP3.
Met criteria codes
PM1
in appropriate head domain region
PM2
absent from gnomAD with good coverage
PP3
BayesDel deleterious
Not Met criteria codes
PM4
missense variant
PM6
No de novo cases reported
PS3
No functional studies available.
PM5
MYH7 p.C905F (PM1, PM2, PP3), p.C905R (PM6_supp,PM1, PM2, PP3), and p.C905Y (PM1, PM2, PP3) are VUS.
PS2
No de novo cases reported
PS4
only 1 HCM proband reported
PS1
No other c. with same p. reported
BA1
absent from gnomAD with good coverage
PVS1
missense variant
BP7
missense variant
BP5
no probands meeting this criterium
BP2
no probands meeting this criterium
BP4
BayesDel deleterious
BS4
No segregation data available.
BS3
No functional studies available.
BS1
absent from gnomAD with good coverage
PP1
No segregation data available.
Approved on: 2021-09-22
Published on: 2021-10-01
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