ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.7994C>T (p.Thr2665Met)

gnomAD frequency: 0.00001  dbSNP: rs151309106
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000622066 SCV000736859 uncertain significance Cardiovascular phenotype 2023-02-16 criteria provided, single submitter clinical testing The p.T2665M variant (also known as c.7994C>T), located in coding exon 24 of the DSP gene, results from a C to T substitution at nucleotide position 7994. The threonine at codon 2665 is replaced by methionine, an amino acid with similar properties. This alteration has been reported in dilated cardiomyopathy (DCM) cohorts; however, clinical details were limited (Kühnisch J et al. Clin Genet, 2019 Dec;96:549-559; Verdonschot JAJ et al. Circ Genom Precis Med, 2020 Oct;13:476-487). This amino acid position is 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 RCV000699495 SCV000828208 likely benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2023-12-01 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001181546 SCV001346720 uncertain significance Cardiomyopathy 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces threonine with methionine at codon 2665 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 been reported in two individuals affected with dilated cardiomyopathy (PMID: 31568572, 32880476). This variant has also been identified in 11/282270 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.
Fulgent Genetics, Fulgent Genetics RCV002483708 SCV002793274 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 2021-11-17 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001529017 SCV004163057 uncertain significance not provided 2023-01-01 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001529017 SCV001741743 uncertain significance not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001529017 SCV001932261 uncertain significance not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001529017 SCV001955740 uncertain significance not provided no assertion criteria provided clinical testing

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