ClinVar Miner

Submissions for variant NM_000335.5(SCN5A):c.5248TTC[1] (p.Phe1751del)

dbSNP: rs2125826148
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003773516 SCV002311979 likely pathogenic not provided 2024-12-12 criteria provided, single submitter clinical testing This variant, c.5254_5256del, results in the deletion of 1 amino acid(s) of the SCN5A protein (p.Phe1752del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with Brugada syndrome (PMID: 38196587; internal data). ClinVar contains an entry for this variant (Variation ID: 1524388). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects SCN5A function (PMID: 38196587). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Roden Lab, Vanderbilt University Medical Center RCV002300646 SCV002588718 likely pathogenic Brugada syndrome 1 2022-11-01 criteria provided, single submitter clinical testing The SCN5A variant c.5254_5256del (p.Phe1752del) NM_198056.2 was observed in an individual with Brugada Syndrome. Functional studies in HEK293T cells showed a complete absence of peak current, using a high-throughput method (PMID: 32533946). The variant is not observed in large population databases (PMID: 32461654). The variant is located in a hotspot region of the protein (transmembrane domain IV of pore-lining helix) (PMID: 32893267). Collectively, this evidence supports a classification of Likely Pathogenic.

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