ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1105G>A (p.Val369Met)

gnomAD frequency: 0.00001  dbSNP: rs730882097
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001179374 SCV001344026 uncertain significance Familial hypercholesterolemia 2022-03-03 criteria provided, single submitter clinical testing This missense variant (also known as p.Val348Met in the mature protein) replaces valine with methionine at codon 369 of the LDLR protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). A functional study has shown that this variant does not disrupt LDL uptake function of the LDLR protein (PMID: 25647241). To our knowledge, this variant has not been reported in individuals affected with familial hypercholesterolemia in the literature. This variant has been identified in 2/251362 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.
GeneDx RCV000161979 SCV002567472 uncertain significance not provided 2022-02-16 criteria provided, single submitter clinical testing Identified in association with early myocardial infarction and familial hypercholesterolemia (FH) in the published literature (Do et al., 2015; Li et al., 2017; Chan et al., 2019); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Published in vitro functional studies showed no effect on LDL uptake (Thormaehlen et al., 2015); This variant is associated with the following publications: (PMID: 30592178, 27932355, 25647241, 25487149)
Fulgent Genetics, Fulgent Genetics RCV002485006 SCV002790326 uncertain significance Hypercholesterolemia, familial, 1 2021-09-04 criteria provided, single submitter clinical testing
Dept. of Genetics and Pharmacogenomics, Merck Research Labs RCV000161979 SCV000189554 not provided not provided no assertion provided in vitro

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