ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.4343G>A (p.Arg1448His) (rs121908545)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000517055 SCV000615099 pathogenic not provided 2014-12-31 criteria provided, single submitter clinical testing
GeneReviews RCV000206992 SCV000262572 pathogenic Hyperkalemic Periodic Paralysis Type 1 no assertion criteria provided literature only
Invitae RCV000206992 SCV000776544 pathogenic Hyperkalemic Periodic Paralysis Type 1 2017-08-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1448 of the SCN4A protein (p.Arg1448His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with paramyotonia congenita in several families (PMID: 1316765, 8005599). Additional individuals affected with paramyotonia congenita have also been reported (PMID: 18337730, 18166706, 27415035). ClinVar contains an entry for this variant (Variation ID: 5899). Experimental studies have shown that this missense change causes the SCN4A channel to inactivate slower than what is observed for wild type channel (PMID: 8110459, 12562902, 7809121). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000006259 SCV000026441 pathogenic Paramyotonia congenita of von Eulenburg 1994-06-01 no assertion criteria provided literature only
Yale Center for Mendelian Genomics,Yale University RCV000662289 SCV000784617 likely pathogenic Rhabdomyolysis 2017-08-05 no assertion criteria provided literature only

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