ClinVar Miner

Submissions for variant NM_001367721.1(CASK):c.1390A>G (p.Thr464Ala)

gnomAD frequency: 0.00001  dbSNP: rs886042221
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) 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.
GeneDx 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

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