Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV001141106 | SCV001301431 | uncertain significance | Isolated Nonsyndromic Congenital Heart Disease | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Labcorp Genetics |
RCV002032345 | SCV002167770 | likely benign | Alagille syndrome due to a JAG1 point mutation | 2023-10-30 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV003353171 | SCV004070710 | uncertain significance | Cardiovascular phenotype | 2023-07-13 | criteria provided, single submitter | clinical testing | The p.R889W variant (also known as c.2665C>T), located in coding exon 22 of the JAG1 gene, results from a C to T substitution at nucleotide position 2665. The arginine at codon 889 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |
Prevention |
RCV004548019 | SCV004103589 | uncertain significance | JAG1-related disorder | 2024-02-01 | no assertion criteria provided | clinical testing | The JAG1 c.2665C>T variant is predicted to result in the amino acid substitution p.Arg889Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0098% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |