ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2359G>A (p.Val787Met)

gnomAD frequency: 0.00003  dbSNP: rs143771219
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001181071 SCV001346143 uncertain significance Familial hypercholesterolemia 2023-05-03 criteria provided, single submitter clinical testing This missense variant (also known as p.Val766Met in the mature protein) replaces valine with methionine at codon 787 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 been reported in an individual affected with ischemic stroke (PMID: 36973604). This variant has been identified in 7/282818 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001181071 SCV001493135 uncertain significance Familial hypercholesterolemia 2022-07-05 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 787 of the LDLR protein (p.Val787Met). This variant is present in population databases (rs143771219, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of familial hypercholesterolemia (Invitae). ClinVar contains an entry for this variant (Variation ID: 430836). 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 methionine 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.
Mayo Clinic Laboratories, Mayo Clinic RCV001509015 SCV001715500 uncertain significance not provided 2019-07-28 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004003491 SCV004820675 uncertain significance Hypercholesterolemia, familial, 1 2024-08-23 criteria provided, single submitter clinical testing This missense variant (also known as p.Val766Met in the mature protein) replaces valine with methionine at codon 787 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 been reported in a South African individual affected with familial hypercholesterolemia, who also carried a pathogenic variant p.Asp221Gly in the same gene (Raal et al., 2018). This variant has been identified in a Japanese control subject in a large myocardial infarction case-control study (PMID: 29802317). This variant has been identified in 7/282818 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, Inc. RCV001181071 SCV002086874 uncertain significance Familial hypercholesterolemia 2020-04-20 no assertion criteria provided clinical testing

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