Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587494 | SCV000698449 | uncertain significance | not provided | 2017-01-23 | criteria provided, single submitter | clinical testing | Variant summary: The DSP c.8117A>T (p.Lys2706Met) variant involves the alteration of a conserved nucleotide. 3/5 in silico tools predict a damaging outcome for this variant. This variant was found in 5/121266 control chromosomes at a frequency of 0.0000412, which is approximately 2 times the estimated maximal expected allele frequency of a pathogenic DSP variant (0.000025), suggesting this variant is possibly a benign polymorphism. However, due to limit number of occurrences in ExAC controls, benign classifcation of this variant can not be unequivocally established. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as VUS. |
Color Diagnostics, |
RCV000772488 | SCV000905667 | uncertain significance | Cardiomyopathy | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with methionine at codon 2706 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 performed for this variant. This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 25351510) and in two brothers affected with dilated cardiomyopathy who also carried a pathogenic variant in the LMNA gene (PMID: 28790152). This variant has been identified in 10/282828 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. |
Labcorp Genetics |
RCV000804647 | SCV000944564 | likely benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2024-01-27 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002497237 | SCV002812182 | 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 | 2021-07-26 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003159999 | SCV003904494 | uncertain significance | Cardiovascular phenotype | 2022-11-09 | criteria provided, single submitter | clinical testing | The p.K2706M variant (also known as c.8117A>T), located in coding exon 24 of the DSP gene, results from an A to T substitution at nucleotide position 8117. The lysine at codon 2706 is replaced by methionine, an amino acid with similar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort; however, clinical details were limited (Lopes LR et al. Heart, 2015 Feb;101:294-301). Additionally, this alteration was detected in a family with dilated cardiomyopathy (DCM), where an additional alteration in LMNA was identified (Hoorntje ET et al. Circ Cardiovasc Genet, 2017 Aug;10:[ePub ahead of print]). 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Mayo Clinic Laboratories, |
RCV000587494 | SCV004227191 | uncertain significance | not provided | 2022-07-12 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV004002439 | SCV004821610 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma | 2024-01-11 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with methionine at codon 2706 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 performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 10/282828 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. |
Gene |
RCV000587494 | SCV005325746 | uncertain significance | not provided | 2023-12-19 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in affected individuals within a family who also harbored a pathogenic LMNA variant; however, the DSP variant showed incomplete segregation with disease (PMID: 28790152); This variant is associated with the following publications: (PMID: 28790152) |
Clinical Molecular Genetics Laboratory, |
RCV000678706 | SCV000804870 | uncertain significance | Primary dilated cardiomyopathy | 2017-08-29 | no assertion criteria provided | clinical testing |