ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2179G>A (p.Val727Ile)

gnomAD frequency: 0.00008  dbSNP: rs769247787
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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 RCV001191575 SCV001359444 uncertain significance Familial hypercholesterolemia 2022-12-05 criteria provided, single submitter clinical testing This missense variant (also known as p.Val706Ile in the mature protein) replaces valine with isoleucine at codon 727 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 two individuals affected with myocardial infarction (PMID: 29802317) and one individual in the healthy control group (PMID: 25487149). This variant has been identified in 13/282596 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 RCV001191575 SCV001412492 uncertain significance Familial hypercholesterolemia 2021-09-08 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 727 of the LDLR protein (p.Val727Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs769247787, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with LDLR-related conditions. 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 isoleucine 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.
All of Us Research Program, National Institutes of Health RCV004010525 SCV004818505 uncertain significance Hypercholesterolemia, familial, 1 2024-05-09 criteria provided, single submitter clinical testing This missense variant (also known as p.Val706Ile in the mature protein) replaces valine with isoleucine at codon 727 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 two individuals affected with myocardial infarction (PMID: 29802317) and one individual in the healthy control group (PMID: 25487149). This variant has been identified in 13/282596 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. RCV001191575 SCV002086863 uncertain significance Familial hypercholesterolemia 2020-02-16 no assertion criteria provided clinical testing

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