ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.2006G>A (p.Arg669His)

gnomAD frequency: 0.00001  dbSNP: rs80338784
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000206926 SCV000813821 pathogenic Hyperkalemic periodic paralysis 2021-12-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 669 of the SCN4A protein (p.Arg669His). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects SCN4A function (PMID: 11102465, 11912116, 21881211, 25024265). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 5911). This missense change has been observed in individual(s) with hypokalemic periodic paralysis (PMID: 10599760, 18162704, 21841462). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs80338784, gnomAD 0.009%).
Athena Diagnostics RCV003482224 SCV004230009 pathogenic not provided 2023-03-21 criteria provided, single submitter clinical testing The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant appears to occur de novo in multiple individuals with clinical features of hypokalemic periodic paralysis. Assessment of experimental evidence suggests this variant results in abnormal protein function. (PMID: 11102465, 11912116, 21881211, 25024265) The variant is located in a region that is considered important for protein function and/or structure.
Fulgent Genetics, Fulgent Genetics RCV005016247 SCV005651801 pathogenic Potassium-aggravated myotonia; Paramyotonia congenita of Von Eulenburg; Hypokalemic periodic paralysis, type 2; Hyperkalemic periodic paralysis; Congenital myasthenic syndrome 16; Congenital myopathy 22A, classic; Congenital myopathy 22B, severe fetal 2024-03-13 criteria provided, single submitter clinical testing
OMIM RCV000006274 SCV000026456 pathogenic Hypokalemic periodic paralysis, type 2 2002-04-01 no assertion criteria provided literature only
GeneReviews RCV000006274 SCV000040614 not provided Hypokalemic periodic paralysis, type 2 no assertion provided literature only
GeneReviews RCV000206926 SCV000262562 not provided Hyperkalemic periodic paralysis no assertion provided literature only

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