ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.2330T>A (p.Phe777Tyr)

dbSNP: rs794728863
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000183001 SCV000235406 uncertain significance not provided 2017-04-06 criteria provided, single submitter clinical testing While the F777Y variant in the SCN5A gene has not been reported to our knowledge, a substitution affecting this same residue, F777L, has been reported in association with familial heart block (Makit N et al., 2012). Additionally, variants in nearby residues (P773S, Q779K) have been reported in association with SCN5A-related disorders, further supporting the functional importance of this residue and this region of the protein. Moreover, F777Y results in a non-conservative amino acid substitution at a position that is completely conserved across species. In silico analysis predicts F777Y is probably damaging to the protein structure/function. Furthermore, F777Y was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Color Diagnostics, LLC DBA Color Health RCV001842906 SCV001356473 uncertain significance Cardiac arrhythmia 2023-12-05 criteria provided, single submitter clinical testing Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the transmembrane domain DII of the SCN5A protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant is rare in the general population and has been identified in 0/277264 chromosomes by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively.
Revvity Omics, Revvity RCV000183001 SCV003821330 uncertain significance not provided 2020-09-24 criteria provided, single submitter clinical testing

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