ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.4312T>C (p.Ser1438Pro)

gnomAD frequency: 0.00001  dbSNP: rs1561698695
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000770240 SCV000901671 uncertain significance Cardiomyopathy 2016-10-26 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000770240 SCV001341992 uncertain significance Cardiomyopathy 2020-09-29 criteria provided, single submitter clinical testing This missense variant replaces serine with proline at codon 1438 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). To our knowledge, functional studies have not been reported 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.
Invitae RCV001242616 SCV001415714 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2024-01-08 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1438 of the DSP protein (p.Ser1438Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 626742). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
GeneDx RCV001766596 SCV001998257 uncertain significance not provided 2019-11-17 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002332550 SCV002633210 uncertain significance Cardiovascular phenotype 2022-05-02 criteria provided, single submitter clinical testing The p.S1438P variant (also known as c.4312T>C), located in coding exon 23 of the DSP gene, results from a T to C substitution at nucleotide position 4312. The serine at codon 1438 is replaced by proline, an amino acid with similar 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.

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