Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000263862 | SCV000353135 | likely benign | Hypokalemic periodic paralysis, type 1 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
Gene |
RCV000484498 | SCV000572370 | uncertain significance | not provided | 2022-06-28 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV000697995 | SCV000826633 | likely benign | Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 | 2023-11-11 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003165797 | SCV003862751 | uncertain significance | Inborn genetic diseases | 2023-02-27 | criteria provided, single submitter | clinical testing | The c.1352C>T (p.S451L) alteration is located in exon 10 (coding exon 10) of the CACNA1S gene. This alteration results from a C to T substitution at nucleotide position 1352, causing the serine (S) at amino acid position 451 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV003517182 | SCV004360394 | uncertain significance | Malignant hyperthermia, susceptibility to, 5 | 2022-11-06 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with leucine at codon 451 of the CACNA1S protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CACNA1S-related disorders in the literature. This variant has been identified in 12/251448 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |