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.4470G>C (p.Glu1490Asp)

CA015001

181390 (ClinVar)

Gene: MYH7
Condition: hypertrophic cardiomyopathy
Inheritance Mode: Autosomal dominant inheritance
UUID: f42ed129-9158-4829-94b0-8537a2253063
Approved on: 2021-09-21
Published on: 2022-04-27

HGVS expressions

NM_000257.4:c.4470G>C
NM_000257.4(MYH7):c.4470G>C (p.Glu1490Asp)
NC_000014.9:g.23417202C>G
CM000676.2:g.23417202C>G
NC_000014.8:g.23886411C>G
CM000676.1:g.23886411C>G
NC_000014.7:g.22956251C>G
NG_007884.1:g.23460G>C
ENST00000355349.4:c.4470G>C
ENST00000355349.3:c.4470G>C
NM_000257.3:c.4470G>C
NR_126491.1:n.652-10C>G
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Uncertain Significance

Met criteria codes 2
PM2 PS4_Supporting
Not Met criteria codes 15
PP1 PP3 PS3 PM6 PM5 PM1 PS2 PS1 BA1 BP5 BP2 BP4 BS4 BS3 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.4470G>C (p.Glu1490Asp) variant has been reported in 2 individuals with HCM (PS4_Supporting; GeneDx pers. comm., LMM pers. comm.). This variant was absent from large population studies (PM2; gnomAD v.2.1.1, http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. 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 (PMID:29300372): PS4_Supporting, PM2.
Met criteria codes
PM2
Variant is absent from gnomAD with adequate coverage.
PS4_Supporting
Per Internal Data Log: 1 HCM proband from GeneDx 1 HCM proband from LMM (proband also had MYBPC3 VUS)
Not Met criteria codes
PP1
none
PP3
REVEL score of 0.632
PS3
None
PM6
none
PM5
none at this position
PM1
outside of approved PM1 domain
PS2
none
PS1
none at this position
BA1
Variant is absent from gnomAD with adequate coverage.
BP5
none
BP2
none
BP4
REVEL score of 0.632
BS4
none
BS3
None
BS1
Variant is absent from gnomAD with adequate coverage.
Curation History
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