Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000041616 | SCV000065312 | likely benign | not specified | 2012-11-07 | criteria provided, single submitter | clinical testing | Arg1116Gln in exon 18 of SCN5A: This variant is not expected to have clinical si gnificance due to a lack of conservation across species, including mammals. Of n ote, multiple mammals, including several primates, have a glutamine (Gln) at thi s position despite high nearby amino acid conservation. In addition, computation al analyses (AlignGVGD, PolyPhen2, SIFT) do not suggest a high likelihood of imp act to the protein. This variant was also identified in 3/4196 African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS/). |
| Gene |
RCV000656974 | SCV000235440 | uncertain significance | not provided | 2024-07-23 | criteria provided, single submitter | clinical testing | Has been reported in association with HCM and intrauterine fetal demise (IUFD) (PMID: 30847666, 23571586); however, this variant has also been reported in a control population (PMID: 25904541); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23631430, 24033266, 23571586, 25904541, 30847666) |
| Labcorp Genetics |
RCV000656974 | SCV000545085 | uncertain significance | not provided | 2025-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1116 of the SCN5A protein (p.Arg1116Gln). This variant is present in population databases (rs369678002, gnomAD 0.04%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 23571586). ClinVar contains an entry for this variant (Variation ID: 48299). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change does not substantially affect SCN5A function (PMID: 23571586). 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, |
RCV001841603 | SCV001346202 | likely benign | Cardiac arrhythmia | 2019-02-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004018915 | SCV004943833 | likely benign | Cardiovascular phenotype | 2020-05-28 | 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. |