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.5530G>A (p.Glu1844Lys)

CA016196

181285 (ClinVar)

Gene: MYH7
Condition: dilated cardiomyopathy
Inheritance Mode: Autosomal dominant inheritance
UUID: 5d6ca7fc-f842-4367-8d3d-f504d92f48c3
Approved on: 2021-10-05
Published on: 2021-10-05

HGVS expressions

NM_000257.4:c.5530G>A
NM_000257.4(MYH7):c.5530G>A (p.Glu1844Lys)
NC_000014.9:g.23415024C>T
CM000676.2:g.23415024C>T
NC_000014.8:g.23884233C>T
CM000676.1:g.23884233C>T
NC_000014.7:g.22954073C>T
NG_007884.1:g.25638G>A
ENST00000355349.4:c.5530G>A
ENST00000355349.3:c.5530G>A
NM_000257.3:c.5530G>A
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Uncertain Significance

Met criteria codes 3
PM2 PS4_Supporting PP3
Not Met criteria codes 17
PM6 PM1 PM4 PM5 BA1 PVS1 BS4 BS3 BS1 BP5 BP2 BP7 BP4 PS2 PS1 PS3 PP1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Cardiomyopathy VCEP
The c.5530G>A (p.Glu1844Lys) variant in MYH7 has been reported in 2 individuals with DCM, 1 individual with HCM and in 1 individual with LVNC (PS4_supporting; Walsh 2017 PMID:27532257, GeneDx pers. comm.). This variant has been identified in 0.0099% (1/10078) of Ashkenazi Jewish chromosomes, but is absent from all other populations in gnomAD v2.1.1 (PM2; http://gnomad.broadinstitute.org). Computational prediction tools and conservation analysis suggest that this variant may impact the protein (PP3). In summary, due to lack of sufficient evidence, this variant meets criteria to be classified as uncertain significance for dilated cardiomyopathy in an autosomal dominant manner. MYH7-specific ACMG/AMP criteria applied (Kelly 2018 PMID:29300372): PP3; PM2; PS4_Supporting
Met criteria codes
PM2
This variant was identified in 0.0099% (1/10078) of Ashkenazi Jewish chromosomes in gnomAD v2.1.1 (PM2; https://gnomad.broadinstitute.org)
PS4_Supporting
Identified in 2 probands with DCM in published literature (PMID 27532257) GeneDx internal data: identified in one proband with HCM; identified in one proband with LVNC and additional VUS in ACTN2
PP3
Borderline revel score, but conserved, SIFT, MUT taster and polyphen all deleterious
Not Met criteria codes
PM6
no evidence
PM1
does not lie in head domain (181-937)
PM4
n/a
PM5
no evidence
BA1
This variant was identified in 0.0099% (1/10078) of Ashkenazi Jewish chromosomes in gnomAD v2.1.1 (PM2; https://gnomad.broadinstitute.org)
PVS1
n/a
BS4
no evidence
BS3
no evidence
BS1
This variant was identified in 0.0099% (1/10078) of Ashkenazi Jewish chromosomes in gnomAD v2.1.1 (PM2; https://gnomad.broadinstitute.org)
BP5
no evidence
BP2
no data
BP7
n/a
BP4
Borderline revel score, but conserved, SIFT, MUT taster and polyphen all deleterious
PS2
no evidence
PS1
no evidence
PS3
no evidence
PP1
no evidence
Curation History
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