ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.4172A>C (p.Tyr1391Ser)

dbSNP: rs727504547
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001191504 SCV001359337 uncertain significance Cardiomyopathy 2020-01-08 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with serine at codon 1391 of the DSP protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002327455 SCV002632733 uncertain significance Cardiovascular phenotype 2019-11-20 criteria provided, single submitter clinical testing The p.Y1391S variant (also known as c.4172A>C), located in coding exon 23 of the DSP gene, results from an A to C substitution at nucleotide position 4172. The tyrosine at codon 1391 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV002560981 SCV002946914 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2022-05-29 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 927931). This variant has not been reported in the literature in individuals affected with DSP-related conditions. This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 1391 of the DSP protein (p.Tyr1391Ser).

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