ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.1949A>G (p.Asn650Ser) (rs145650440)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000038003 SCV000061669 uncertain significance not specified 2013-10-14 criteria provided, single submitter clinical testing The Asn650Ser variant in DSP has now been identified by our laboratory in 2 Blac k individuals with HCM, 1 of whom carried a pathogenic variant in another gene. This variant has also been identified in 1/4406 African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs1 45650440). Computational analyses (biochemical amino acid properties, conservati on, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. In summary, additional information is needed to fully assess the clinical significance of this variant.
Invitae RCV000469452 SCV000543271 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-11-01 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 650 of the DSP protein (p.Asn650Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs145650440, ExAC 0.04%). This variant has not been reported in the literature in individuals with DSP-related disease. ClinVar contains an entry for this variant (Variation ID: 44869). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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