ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.3760G>A (p.Val1254Ile)

gnomAD frequency: 0.00003  dbSNP: rs778448699
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000705333 SCV000834325 likely benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2025-01-12 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001184094 SCV001349996 uncertain significance Cardiomyopathy 2023-10-12 criteria provided, single submitter clinical testing This missense variant replaces valine with isoleucine at codon 1254 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 been identified in 8/250684 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 RCV002343560 SCV002622327 uncertain significance Cardiovascular phenotype 2024-10-16 criteria provided, single submitter clinical testing The p.V1254I variant (also known as c.3760G>A), located in coding exon 23 of the DSP gene, results from a G to A substitution at nucleotide position 3760. The valine at codon 1254 is replaced by isoleucine, an amino acid with highly 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. Based on the available evidence, the clinical significance of this variant remains unclear.
All of Us Research Program, National Institutes of Health RCV003999766 SCV004839441 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma 2024-01-11 criteria provided, single submitter clinical testing This missense variant replaces valine with isoleucine at codon 1254 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 been identified in 8/250684 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.

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