Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000038070 | SCV000061736 | uncertain significance | not specified | 2012-04-10 | criteria provided, single submitter | clinical testing | The Leu1971Pro variant (DSP) has not been reported in the literature nor previou sly identified by our laboratory. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that this var iant may impact the protein, though this information is not predictive enough to determine pathogenicity. Additional information is needed to fully assess the c linical significance of the Leu1971Pro variant. |
| Invitae | RCV000688727 | SCV000816350 | benign | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2022-04-28 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000038070 | SCV000919291 | uncertain significance | not specified | 2017-10-23 | criteria provided, single submitter | clinical testing | Variant summary: The DSP c.5912T>C (p.Leu1971Pro) variant involves the alteration of a conserved nucleotide and 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). However, these predictions have yet to be functionally assessed. This variant was found in 4/277060 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.000167 (4/23994). This frequency is about 7 times the estimated maximal expected allele frequency of a pathogenic DSP variant (0.000025), suggesting this is likely a benign polymorphism found primarily in the populations of African origin, although the allele count is small. An internal LCA sample also carried a pathogenic variant in TTR c.424G>A/p.Val142Ile, further supporting the non-pathogenic role of the variant of interest. In addition, one other clinical diagnostic laboratory classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a "Variant of Uncertain Significance (VUS) - Possibly Benign," until additional information becomes available. |
| Mayo Clinic Laboratories, |
RCV001509261 | SCV001715874 | uncertain significance | not provided | 2021-03-23 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003298072 | SCV003997433 | uncertain significance | Cardiovascular phenotype | 2023-03-27 | criteria provided, single submitter | clinical testing | The p.L1971P variant (also known as c.5912T>C), located in coding exon 24 of the DSP gene, results from a T to C substitution at nucleotide position 5912. The leucine at codon 1971 is replaced by proline, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |