Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV005222913 | SCV005863470 | pathogenic | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2024-03-20 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 622 of the DSP protein (p.Leu622Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant DSP-related cardiomyopathy with wooly hair and palmoplantar keratoderma syndrome (PMID: 26604139, 26833927). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 372127). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects DSP function (PMID: 26604139). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000412530 | SCV000490196 | pathogenic | Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis | 2016-11-22 | no assertion criteria provided | literature only |