ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.3814G>A (p.Asp1272Asn) (rs730880906)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158860 SCV000208795 likely pathogenic not provided 2011-10-18 criteria provided, single submitter clinical testing This missense variant is denoted p.Asp1272Asn (D1272N) at the protein level and c.3814 G>A at the cDNA level. The Asp1272Asn variant in the MYH7 gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. Asp1272Asn results in a semi-conservative amino acid substitution of a negatively charged Aspartic acid with a neutral, polar Asparagine at a residue that is conserved across species. In silico analysis predicts Asp1272Asn is possibly damaging to the protein structure/function. The Asp1272Asn variant was not detected in up to 200 alleles from control individuals of Caucasian ancestry tested at GeneDx, indicating it is not a common benign variant in this population. The variant is found in HCM panel(s).
Invitae RCV000821381 SCV000962136 uncertain significance Hypertrophic cardiomyopathy 2018-11-21 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 1272 of the MYH7 protein (p.Asp1272Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs730880906, ExAC 0.03%). This variant has not been reported in the literature in individuals with MYH7-related disease. ClinVar contains an entry for this variant (Variation ID: 181385). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; 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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