Total submissions: 14
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001034632 | SCV000285015 | pathogenic | Familial hypercholesterolemia | 2020-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 540 of the LDLR protein (p.Ala540Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs769370816, ExAC 0.01%). This variant has been observed in individual(s) with familial hypercholesterolemia and hyperlipidemia (PMID: 9544745, 11196104, 15200491, 15241806, 18718593, 21376320, 23375686, 24075752, 25461735, 19007590). It has also been observed to segregate with disease in related individuals. This variant is also known as A519T in the literature. ClinVar contains an entry for this variant (Variation ID: 226363). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). For these reasons, this variant has been classified as Pathogenic. |
LDLR- |
RCV000211624 | SCV000295541 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Cardiovascular Research Group, |
RCV000211624 | SCV000322966 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | 0/190 non-FH alleles |
Robarts Research Institute, |
RCV000211624 | SCV000484729 | likely pathogenic | Familial hypercholesterolemia 1 | criteria provided, single submitter | clinical testing | ||
Centre de Génétique Moléculaire et Chromosomique, |
RCV000211624 | SCV000503376 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subjects mutated among 2600 FH index cases screened = 4 (2 homozygotes), family members 1 (1 homozygote) with co-segregation) / previously described in association with FH/Software predictions: Conflicting |
Molecular Genetics Laboratory, |
RCV000211624 | SCV000540827 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-11-05 | criteria provided, single submitter | clinical testing | |
U4M - |
RCV000211624 | SCV000583853 | pathogenic | Familial hypercholesterolemia 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Laboratory of Genetics and Molecular Cardiology, |
RCV000211624 | SCV000588598 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
Fundacion Hipercolesterolemia Familiar | RCV000211624 | SCV000607618 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
Ce |
RCV000996756 | SCV001151664 | likely pathogenic | not provided | 2019-05-01 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV001034632 | SCV001339063 | pathogenic | Familial hypercholesterolemia | 2020-03-30 | criteria provided, single submitter | clinical testing | Variant summary: LDLR c.1618G>A (p.Ala540Thr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 251472 control chromosomes. c.1618G>A has been reported in the literature in multiple individuals affected with Hypercholesterolemia (Sun_1998, Merino-Ibarra_2007, Bertolini_2013, Martin_2016). These data indicate that the variant is very likely to be associated with disease. Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Brunham Lab, |
RCV000211624 | SCV001432660 | pathogenic | Familial hypercholesterolemia 1 | 2019-03-10 | criteria provided, single submitter | research | |
Cardiovascular Genetics Laboratory, |
RCV000211624 | SCV000268625 | pathogenic | Familial hypercholesterolemia 1 | 2011-04-08 | no assertion criteria provided | clinical testing | |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000211624 | SCV000606468 | pathogenic | Familial hypercholesterolemia 1 | no assertion criteria provided | research |