ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.5375C>T (p.Pro1792Leu)

gnomAD frequency: 0.00002  dbSNP: rs750560473
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000794993 SCV000934431 uncertain significance Hyperkalemic periodic paralysis 2023-06-23 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with SCN4A-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SCN4A protein function. ClinVar contains an entry for this variant (Variation ID: 641693). This variant is present in population databases (rs750560473, gnomAD 0.006%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1792 of the SCN4A protein (p.Pro1792Leu).
Ambry Genetics RCV002536990 SCV003754472 uncertain significance Inborn genetic diseases 2021-10-05 criteria provided, single submitter clinical testing The c.5375C>T (p.P1792L) alteration is located in exon 24 (coding exon 24) of the SCN4A gene. This alteration results from a C to T substitution at nucleotide position 5375, causing the proline (P) at amino acid position 1792 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003396380 SCV004105245 uncertain significance SCN4A-related condition 2023-09-04 criteria provided, single submitter clinical testing The SCN4A c.5375C>T variant is predicted to result in the amino acid substitution p.Pro1792Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0065% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-62018267-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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