ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.1112A>C (p.His371Pro) (rs397516912)

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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 RCV000037984 SCV000061650 uncertain significance not specified 2012-03-22 criteria provided, single submitter clinical testing The His371Pro variant (DSP) has not been reported in the literature nor previous ly identified by our laboratory. Variants in DSP have been reported in individu als with ARVC. Computational analyses (biochemical amino acid properties, conse rvation, AlignGVGD, PolyPhen2, and SIFT) suggest that this variant may impact th e protein, though this information is not predictive enough to determine pathoge nicity. Additional studies are needed to fully assess its clinical significance.
Invitae RCV000464608 SCV000543245 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2016-11-24 criteria provided, single submitter clinical testing This sequence change replaces histidine with proline at codon 371 of the DSP protein (p.His371Pro). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and proline. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a DSP-related disease. ClinVar contains an entry for this variant (Variation ID: 44851). 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, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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