Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000587603 | SCV000697224 | uncertain significance | not provided | 2017-08-03 | criteria provided, single submitter | clinical testing | Variant summary: The LDLR c.2273G>C (p.Gly758Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in the large control database ExAC in 2/120684 control chromosomes at a frequency of 0.0000166, which does not exceed the estimated maximal expected allele frequency of a pathogenic LDLR variant (0.0012508). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS). |
| Labcorp Genetics |
RCV001829627 | SCV002266858 | benign | Familial hypercholesterolemia | 2024-10-29 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004807024 | SCV005427650 | uncertain significance | Hypercholesterolemia, familial, 1 | 2024-07-20 | criteria provided, single submitter | clinical testing | This missense variant (also known as p.Gly737Ala in the mature protein) replaces glycine with alanine at codon 758 of the LDLR protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with LDLR-related disorders in the literature. This variant has been identified in 5/251262 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Natera, |
RCV001829627 | SCV002086871 | uncertain significance | Familial hypercholesterolemia | 2019-10-28 | no assertion criteria provided | clinical testing |