ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.5707C>A (p.Gln1903Lys) (rs794728103)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181263 SCV000233548 uncertain significance not provided 2016-02-03 criteria provided, single submitter clinical testing The Q1903K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The Q1903K variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q1903K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis predicts this variant likely does not alter the protein structure/function.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. This result cannot be interpreted for diagnosis or used for family member screening at this time.
Invitae RCV000554349 SCV000641324 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2017-05-09 criteria provided, single submitter clinical testing This sequence change replaces glutamine with lysine at codon 1903 of the DSP protein (p.Gln1903Lys). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and lysine. 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: 199843). 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: "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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