ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.2863G>A (p.Asp955Asn) (rs886039204)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000251778 SCV000320640 likely pathogenic Cardiovascular phenotype 2015-12-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Good segregation with disease (lod 1.5-3 = 5-9 meioses),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation
Invitae RCV000552105 SCV000623686 uncertain significance Hypertrophic cardiomyopathy 2018-09-21 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 955 of the MYH7 protein (p.Asp955Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with left ventricular non-compaction cardiomyopathy (LVNC) in a family (PMID: 17947214) and was reported in at least one individual with dilated cardiomyopathy (PMID: 23349452). However, in both reports this variant was shown to occur in combination with another MYH7 variant, p.Asp545Asn, and in the familial study these variants were confirmed to be on the same chromosome (in cis). Additionally, both variants were also reported in a study of individuals affected with LVNC. It is not clear if the variants were observed in the same individual (PMID: 20965760). ClinVar contains an entry for this variant (Variation ID: 264608). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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