Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000171697 | SCV000050716 | uncertain significance | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Labcorp Genetics |
RCV000171697 | SCV000545065 | uncertain significance | not provided | 2023-11-22 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1738 of the SCN5A protein (p.Ser1738Phe). This variant is present in population databases (rs786205271, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SCN5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 191499). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
Cirak Lab, |
RCV000855502 | SCV000996632 | likely pathogenic | Fetal akinesia deformation sequence 1; Arthrogryposis multiplex congenita | 2019-06-28 | criteria provided, single submitter | research | |
Color Diagnostics, |
RCV001842522 | SCV001346219 | uncertain significance | Cardiac arrhythmia | 2023-02-16 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with phenylalanine at codon 1738 of the SCN5A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been observed in an individual affected with fetal akinesia (PMID: 31680123). This variant has been identified in 1/250758 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. |
All of Us Research Program, |
RCV001842522 | SCV004819795 | uncertain significance | Cardiac arrhythmia | 2023-08-08 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with phenylalanine at codon 1738 of the SCN5A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been observed in an individual affected with fetal akinesia (PMID: 31680123). This variant has been identified in 1/250758 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. |