Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001267059 | SCV001445240 | likely pathogenic | Inborn genetic diseases | 2019-09-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002436986 | SCV002753164 | likely pathogenic | Cardiovascular phenotype | 2019-09-12 | criteria provided, single submitter | clinical testing | The p.E101G variant (also known as c.302A>G), located in coding exon 3 of the LDLR gene, results from an A to G substitution at nucleotide position 302. The glutamic acid at codon 101 is replaced by glycine, an amino acid with similar properties. This alteration impacts a residue in the conserved cluster of acidic amino acids at the C-terminal end of LDLR class A repeat 2 (Jeon H and Blacklow C. Annu. Rev. Biochem. 2005;74:535-62). Internal structural analysis indicates that this alteration eliminates a clinically significant calcium-binding site (Rudenko G et al. Science, 2002 Dec;298:2353-8). A disease-causing mutation, p.E101K, has been described in the same codon (Loux N et al. Hum. Mutat., 1992;1:325-32). This amino acid position is highly 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. |