Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003330810 | SCV000698454 | uncertain significance | not specified | 2023-08-21 | criteria provided, single submitter | clinical testing | Variant summary: DSP c.946A>G (p.Met316Val) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 250602 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.946A>G has been reported in the literature in individuals affected with sudden unexpected death (examples: Campuzano_2014, and Sanchez_2016). These report(s) do not provide unequivocal conclusions about association of the variant with Arrhythmia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 25447171, 27930701). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=3) and likely benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Invitae | RCV000795477 | SCV000934941 | likely benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-12-30 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV001188903 | SCV001356078 | uncertain significance | Cardiomyopathy | 2023-12-18 | criteria provided, single submitter | clinical testing | This missense variant replaces methionine with valine at codon 316 of the DSP protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with sudden cardiac death (PMID: 25447171) and in at least one individual affected with dilated cardiomyopathy (PMID: 37904629). This variant has been identified in 5/250602 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 | RCV002377217 | SCV002688331 | uncertain significance | Cardiovascular phenotype | 2020-12-03 | criteria provided, single submitter | clinical testing | The p.M316V variant (also known as c.946A>G), located in coding exon 8 of the DSP gene, results from an A to G substitution at nucleotide position 946. The methionine at codon 316 is replaced by valine, an amino acid with highly similar properties. This variant has been detected in a sudden unexpected death case which also had other cardiac gene variants (Campuzano O et al. Forensic Sci Int, 2014 12;245:30-7). This amino acid position is highly conserved in available vertebrate species. 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. |
| Fulgent Genetics, |
RCV002497238 | SCV002815012 | 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 | 2021-08-10 | criteria provided, single submitter | clinical testing |