Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000039444 | SCV000063128 | uncertain significance | not specified | 2012-11-30 | criteria provided, single submitter | clinical testing | The His298Leu variant in DSC2 has not been reported in the literature nor previo usly identified by our laboratory. Computational analyses (biochemical amino aci d properties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Histidine (His) at position 298 is not wel l conserved in evolution, suggesting that a change to this position may be toler ated. However, additional information is needed to fully assess the clinical sig nificance of the His298Leu variant. |
Color Diagnostics, |
RCV001184220 | SCV001350160 | uncertain significance | Cardiomyopathy | 2023-05-10 | criteria provided, single submitter | clinical testing | This missense variant replaces histidine with leucine at codon 298 of the DSC2 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 not been reported in individuals affected with DSC2-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. |