Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000171092 | SCV000223657 | uncertain significance | not provided | 2014-01-20 | criteria provided, single submitter | clinical testing | The F176L variant in the SNTA1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The F176L variant is a semi-conservative amino acid substitution as these residues share similar properties, but differ in size, charge, or other properties which may impact secondary structure. In silico analysis predicts F176L is possibly damaging to the protein structure/function. The F176L variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, no mutations in nearby residues have been reported in association with LQTS, suggesting that this region of the protein may be tolerant to change. With the clinical and molecular information available at this time, we cannot definitively determine if F176L is a disease-causing mutation or a rare benign variant. The pathogenic role for this variant would be further supported if it occurred de novo in an individual or if it co-segregates with an LQTS phenotype in a family. The variant is found in LQT panel(s). |
Fulgent Genetics, |
RCV000765488 | SCV000896784 | uncertain significance | Long QT syndrome 12 | 2022-05-31 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001852056 | SCV002190610 | uncertain significance | Long QT syndrome | 2022-07-19 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with SNTA1-related conditions. This variant is present in population databases (rs781703999, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 176 of the SNTA1 protein (p.Phe176Leu). ClinVar contains an entry for this variant (Variation ID: 190909). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. |
Ambry Genetics | RCV003298203 | SCV003988575 | likely benign | Cardiovascular phenotype | 2023-04-17 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |