ClinVar Miner

Submissions for variant NM_002471.3(MYH6):c.4999G>A (p.Asp1667Asn) (rs758251388)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000647052 SCV000768839 uncertain significance Familial hypertrophic cardiomyopathy 14 2017-08-24 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 1667 of the MYH6 protein (p.Asp1667Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs758251388, ExAC 0.02%). This variant has not been reported in the literature in individuals with MYH6-related disease. ClinVar contains an entry for this variant (Variation ID: 312848). 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: "Tolerated"; PolyPhen-2: "Possibly 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.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000756391 SCV000884188 uncertain significance not specified 2019-05-11 criteria provided, single submitter clinical testing The MYH6 c.4999G>A; p.Asp1667Asn variant (rs758251388), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 312848). This variant is found in the general population with an overall allele frequency of 0.004% (12/282842 alleles) in the Genome Aggregation Database. The aspartate at codon 1667 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, due to limited information, the clinical significance of the p.Asp1667Asn variant is uncertain at this time.

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