ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.4991T>G (p.Leu1664Arg)

gnomAD frequency: 0.00002  dbSNP: rs746139953
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002041712 SCV002115281 likely benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2022-12-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV002343883 SCV002645669 uncertain significance Cardiovascular phenotype 2022-03-25 criteria provided, single submitter clinical testing The p.L1664R variant (also known as c.4991T>G), located in coding exon 23 of the DSP gene, results from a T to G substitution at nucleotide position 4991. The leucine at codon 1664 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV004009176 SCV004819677 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma 2023-10-30 criteria provided, single submitter clinical testing This missense variant replaces leucine with arginine at codon 1664 of the DSP protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with arrhythmia and cardiomyopathy (PMID: 33029862). This variant has been identified in 5/250700 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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