ClinVar Miner

Submissions for variant NM_006514.3(SCN10A):c.1715C>T (p.Pro572Leu) (rs553784643)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000658465 SCV000780237 uncertain significance not provided 2018-06-04 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN10A gene. The P572L variant has not been published as pathogenic or been reported as benign to our knowledge. It is classified as a variant of uncertain significance in ClinVar by another clinical laboratory (SCV000547178.2; Landrum et al., 2016). This variant is observed at a global allele frequency of 13/214918 (0.006%) alleles in large population cohorts, including 4/14804 (0.03%) alleles from individuals of East Asian ancestry (Lek et al., 2016). The P572L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function.
Invitae RCV000466540 SCV000547178 uncertain significance Brugada syndrome 2016-12-21 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 572 of the SCN10A protein (p.Pro572Leu). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs553784643, ExAC 0.03%) but has not been reported in the literature in individuals with a SCN10A-related disease. 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 leucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.