Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000181286 | SCV000233576 | uncertain significance | not specified | 2017-03-27 | criteria provided, single submitter | clinical testing | The I368F variant in the DSP gene has not been published as a pathogenic variant or been reported as a benign variant to our knowledge, but it has been previously identified in multiple relatives in one family referred for genetic testing at GeneDx, though limited clinical information is available. The I368F variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Although the I368F variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties, this substitution occurs at a position that is conserved across species. Consequently, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Only one definitive missense variant in a nearby residue (N375I) has been reported in the Human Gene Mutation Database in association with ARVC (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign. |
Ambry Genetics | RCV000617850 | SCV000738191 | uncertain significance | Cardiovascular phenotype | 2023-01-03 | criteria provided, single submitter | clinical testing | The p.I368F variant (also known as c.1102A>T), located in coding exon 9 of the DSP gene, results from an A to T substitution at nucleotide position 1102. The isoleucine at codon 368 is replaced by phenylalanine, an amino acid with highly similar 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. |
Invitae | RCV001240538 | SCV001413492 | likely benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2023-11-07 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001526098 | SCV001736374 | uncertain significance | Cardiomyopathy | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with phenylalanine at codon 368 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 been identified in 1/31402 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. |