Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000369557 | SCV000332652 | uncertain significance | not provided | 2015-07-14 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002313997 | SCV000848722 | uncertain significance | Inborn genetic diseases | 2017-01-10 | criteria provided, single submitter | clinical testing | The p.T464A variant (also known as c.1390A>G), located in coding exon 15 of the CASK gene, results from an A to G substitution at nucleotide position 1390. The threonine at codon 464 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV001238872 | SCV001411705 | uncertain significance | Intellectual disability, CASK-related, X-linked | 2023-09-10 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 464 of the CASK protein (p.Thr464Ala). This variant is present in population databases (no rsID available, gnomAD 0.004%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with CASK-related conditions. ClinVar contains an entry for this variant (Variation ID: 281721). 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 CASK protein function. |
Gene |
RCV000369557 | SCV001872855 | likely benign | not provided | 2021-09-30 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |