Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000541681 | SCV000641280 | benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2022-11-15 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV001179633 | SCV001344342 | uncertain significance | Cardiomyopathy | 2024-01-05 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glycine at codon 345 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 12/250782 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. |
Stanford Center for Inherited Cardiovascular Disease, |
RCV000786124 | SCV000924786 | uncertain significance | not provided | 2017-08-01 | no assertion criteria provided | provider interpretation | Invitae performed testing for this patient. Given the lack of case data, frequency in gnomAD and type of variant, we consider this variant a variant of uncertain significance, probably benign and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). I could find no reports of this variant in Google or PubMed. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change. It should be noted that few missense variants in DSP are thought to be pathogenic. ExAC constraints indicate this gene is tolerant to missense variation (Z=0.91). The variant has been seen in 12 of 122792 individuals listed in the Genome Aggregation Consortium Dataset (gnomAD; http://gnomad.broadinstitute.org/), which currently includes variant calls on >140,000 unrelated individuals of African, Asian, European, Latino, and Ashkenazi descent. The variant has been seen in 10 of 8614 East Asian Individuals (MAF = 0.058%). The site is well covered in ExAC. |