Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000617956 | SCV000736923 | uncertain significance | Cardiovascular phenotype | 2017-09-22 | criteria provided, single submitter | clinical testing | The p.E745A variant (also known as c.2234A>C), located in coding exon 16 of the DSP gene, results from an A to C substitution at nucleotide position 2234. The glutamic acid at codon 745 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Color Diagnostics, |
RCV001185563 | SCV001351812 | uncertain significance | Cardiomyopathy | 2021-04-13 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with alanine at codon 745 of the DSP protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, 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 not been identified 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 |
RCV001868106 | SCV002222826 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2020-12-14 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 519035). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with alanine at codon 745 of the DSP protein (p.Glu745Ala). The glutamic acid residue is highly conserved and there is a moderate physicochemical difference between glutamic acid and alanine. |
| All of Us Research Program, |
RCV004807039 | SCV005428853 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma | 2024-02-22 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with alanine at codon 745 of the DSP protein. Computational prediction tools indicate that this variant has a deleterious impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with DSP-related disorders in the literature. This variant has not been identified 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. |