ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.5412G>T (p.Gln1804His) (rs779809935)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000586786 SCV000698440 uncertain significance not provided 2017-05-19 criteria provided, single submitter clinical testing Variant summary: The DSP c.5412G>T (p.Gln1804His) variant involves the alteration of a non-conserved nucleotide, resulting in a missense substitution. The variant is not located within a known functional domain (InterPro). 3/4 in silico tools predict a benign outcome for this variant. This variant was found in the large control database ExAC in 4 of 121308 control chromosomes from all ethnicities, but was observed exclusively in the Latino subpopulation at a frequency of 0.000346 (4/11576). This frequency is about 14 times the estimated maximal expected allele frequency of a pathogenic DSP variant (0.000025), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. To our knowledge, the variant of interest has not been reported in affected individuals via publications, nor has it been evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as a VUS - possibly benign variant until additional evidence becomes available.
Invitae RCV000641780 SCV000763429 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2017-09-05 criteria provided, single submitter clinical testing This sequence change replaces glutamine with histidine at codon 1804 of the DSP protein (p.Gln1804His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs779809935, ExAC 0.03%). This variant has not been reported in the literature in individuals with DSP-related disease. 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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