Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000472470 | SCV000543266 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with serine at codon 1217 of the DSP protein (p.Thr1217Ser). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and serine. This variant is present in population databases (rs770484693, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with DSP-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Color Diagnostics, |
RCV001189983 | SCV001357384 | uncertain significance | Cardiomyopathy | 2023-03-16 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with serine at codon 1217 of the DSP protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 1/251162 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. |
Mayo Clinic Laboratories, |
RCV003480637 | SCV004227189 | uncertain significance | not provided | 2022-02-15 | criteria provided, single submitter | clinical testing | BP4 |