ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.7855A>G (p.Ile2619Val)

gnomAD frequency: 0.00001  dbSNP: rs767630308
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208491 SCV000263882 uncertain significance Long QT syndrome 2015-10-07 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000703317 SCV000832214 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2024-11-24 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2619 of the DSP protein (p.Ile2619Val). This variant is present in population databases (rs767630308, gnomAD 0.002%). This missense change has been observed in individual(s) with unexplained cardiac arrest (PMID: 35352813). ClinVar contains an entry for this variant (Variation ID: 222586). 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 disruptive. 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.
Color Diagnostics, LLC DBA Color Health RCV001178634 SCV001343133 uncertain significance Cardiomyopathy 2023-03-31 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 2619 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 DSP-related disorders in the literature. This variant has been identified in 2/250864 chromosomes 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 RCV002408904 SCV002669305 uncertain significance Cardiovascular phenotype 2022-07-19 criteria provided, single submitter clinical testing The p.I2619V variant (also known as c.7855A>G), located in coding exon 24 of the DSP gene, results from an A to G substitution at nucleotide position 7855. The isoleucine at codon 2619 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
Fulgent Genetics, Fulgent Genetics RCV002478747 SCV002782038 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8; Lethal acantholytic epidermolysis bullosa; Woolly hair-skin fragility syndrome; Keratosis palmoplantaris striata 2; Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis 2022-02-14 criteria provided, single submitter clinical testing

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