Total submissions: 3
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. |
Prevention |
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. |