Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000237142 | SCV002817168 | uncertain significance | Hypercholesterolemia, familial, 1 | 2022-04-29 | reviewed by expert panel | curation | NM_000527.5(LDLR):c.4G>C (p.Gly2Arg)variant is classified as uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence code PM2 and PP4 as defined by the ClinGen Familial NM_000527.5(LDLR):c.4G>C (p.Gly2Arg)variant is classified as uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence code PM2 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PM2 - PopMax MAF = 0.00016 (0.016%) in African exomes (gnomAD v2.1.1). PP4 - Variant meets PM2 and is identified in one index cases who fulfills SB criteria for FH (1 case from CGMC, UFGOD (APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière)). |
LDLR- |
RCV000237142 | SCV000294410 | likely benign | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Laboratory of Genetics and Molecular Cardiology, |
RCV000237142 | SCV000588479 | uncertain significance | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | |
Color Diagnostics, |
RCV001182216 | SCV001347575 | likely benign | Familial hypercholesterolemia | 2019-02-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001182216 | SCV002225591 | uncertain significance | Familial hypercholesterolemia | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 2 of the LDLR protein (p.Gly2Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs5931, ExAC 0.02%). This missense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 11933210, 25461735). ClinVar contains an entry for this variant (Variation ID: 250971). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |