Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000238215 | SCV000295366 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Cardiovascular Research Group, |
RCV000238215 | SCV000322943 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | 0/208 non-FH alleles; 0/100 healthy control individuals |
Robarts Research Institute, |
RCV000238215 | SCV000484727 | likely pathogenic | Hypercholesterolemia, familial, 1 | criteria provided, single submitter | clinical testing | ||
Ambry Genetics | RCV003298315 | SCV004000127 | likely pathogenic | Cardiovascular phenotype | 2023-05-25 | criteria provided, single submitter | clinical testing | The p.Y442C variant (also known as c.1325A>G), located in coding exon 9 of the LDLR gene, results from an A to G substitution at nucleotide position 1325. The tyrosine at codon 442 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration, which is also known as p.Y421C, has been reported in individuals with familial hypercholesterolemia (FH) (Wang J et al. J Lipid Res, 2005 Feb;46:366-72; Medeiros AM et al. Atherosclerosis, 2010 Oct;212:553-8; Tada H et al. J Clin Lipidol, 2020 Mar;14:346-351.e9; Ambry internal data). Another alteration at the same codon, p.Y442H (c.1324T>C), has been detected in individuals with definite or suspected FH (Widhalm K et al. J Inherit Metab Dis, 2007 Apr;30:239-47; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000238215 | SCV000606394 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |