ClinVar Miner

Submissions for variant NM_174934.4(SCN4B):c.617C>T (p.Ser206Leu)

gnomAD frequency: 0.00009  dbSNP: rs140348243
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000171568 SCV000050612 uncertain significance SUDDEN INFANT DEATH SYNDROME 2018-04-05 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV000234662 SCV000291592 uncertain significance Long QT syndrome 10 2024-09-03 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 206 of the SCN4B protein (p.Ser206Leu). This variant is present in population databases (rs140348243, gnomAD 0.01%). This missense change has been observed in individual(s) with sudden infant death and/or atrial fibrillation (PMID: 20226894, 30821358, 31043699). ClinVar contains an entry for this variant (Variation ID: 191380). 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. Experimental studies have shown that this missense change affects SCN4B function (PMID: 20226894). 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.
GeneDx RCV000490150 SCV000577627 uncertain significance not provided 2024-06-24 criteria provided, single submitter clinical testing Reported in five-month-old male with sudden infant death syndrome (SIDS), and a 61-year-old male reported to have a QTc interval of 452 msec (PMID: 20226894, 23861362); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Functional studies performed in two different model expression systems show that p.(S206L) alters cardiac sodium channel function by accentuating the late sodium current (PMID: 20226894); Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (PMID: 25741868); This variant is associated with the following publications: (PMID: 23861362, 21215473, 21454796, 23304551, 23604097, 23465283, 31043699, 30821358, 34722422, 20226894)
Ambry Genetics RCV002354426 SCV002656844 likely benign Cardiovascular phenotype 2023-02-22 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.
Fulgent Genetics, Fulgent Genetics RCV000234662 SCV002785970 uncertain significance Long QT syndrome 10 2021-08-31 criteria provided, single submitter clinical testing

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