ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.2411C>T (p.Ser804Phe) (rs121908546)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489309 SCV000577654 likely pathogenic not provided 2015-08-07 criteria provided, single submitter clinical testing The S804F variant in the SCN4A gene has been reported in a family segregating an autosomal dominant form of myotonia with overlapping features of paramyotonia congenita and myotonia congenita. This variant was found to co-segregate with the phenotype in all family members tested and was not observed in 100 control chromosomes (McClatchey et al., 1992). The S804F variant was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S804F variant is a non-conservative amino acid substitution, which occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. A missense variant in a nearby residue (A799S) has been reported in the Human Gene Mutation Database in association with severe neonatal episodic laryngospasm (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret S804F as a strong candidate for a disease-causing variant; however, the possibility it may be a rare benign variant cannot be excluded
OMIM RCV000006261 SCV000026443 pathogenic Paramyotonia congenita/myotonia congenita 1994-11-01 no assertion criteria provided literature only
OMIM RCV000006262 SCV000026444 pathogenic Potassium aggravated myotonia 1994-11-01 no assertion criteria provided literature only

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