Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000238540 | SCV000295190 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000238540 | SCV000503292 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subject mutated among 2600 FH index cases screened = 1 /FH-Austria / Software predictions: Damaging |
Molecular Genetics Laboratory, |
RCV000238540 | SCV000540787 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-11-05 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004639192 | SCV005135987 | likely pathogenic | Cardiovascular phenotype | 2024-03-26 | criteria provided, single submitter | clinical testing | The p.D354A variant (also known as c.1061A>C) is located in coding exon 8 of the LDLR gene. The aspartic acid at codon 354 is replaced by alanine, an amino acid with dissimilar properties. This change occurs in the first base pair of coding exon 8. This alteration has been reported in association with familial hypercholesterolemia (FH) (Marduel M et al. Hum Mutat, 2010 Nov;31:E1811-24; Tichý L et al. Atherosclerosis, 2012 Aug;223:401-8). Another variant at the same codon, p.D354G (c.1061A>G), has also been detected in subjects with FH (Hobbs HH et al. Hum Mutat, 1992;1:445-66). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |