ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2506G>A (p.Val836Ile)

dbSNP: rs879255220
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237637 SCV000296025 likely benign Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000456063 SCV000539512 uncertain significance not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 1 paper in HGMD; Absent from ExAC with good coverage
Mayo Clinic Laboratories, Mayo Clinic RCV001509016 SCV001715501 uncertain significance not provided 2019-09-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV002429178 SCV002742365 uncertain significance Cardiovascular phenotype 2022-04-20 criteria provided, single submitter clinical testing The p.V836I variant (also known as c.2506G>A), located in coding exon 17 of the LDLR gene, results from a G to A substitution at nucleotide position 2506. The valine at codon 836 is replaced by isoleucine, an amino acid with highly similar properties. This variant has been reported in familial hypercholesterolemia (FH) cohorts; however, clinical details were limited (Fouchier SW et al. Hum. Mutat., 2005 Dec;26:550-6; Leigh SE et al. Ann. Hum. Genet., 2008 Jul;72:485-98). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV001509016 SCV003927449 uncertain significance not provided 2023-05-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Also known as p.V815I; This variant is associated with the following publications: (PMID: 18325082, 22079632, 34426522, 16250003)
Color Diagnostics, LLC DBA Color Health RCV003581646 SCV004359074 uncertain significance Familial hypercholesterolemia 2023-07-24 criteria provided, single submitter clinical testing This missense variant (also known as p.Val815Ile in the mature protein) replaces valine with isoleucine at codon 836 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 at least one individual affected with familial hypercholesterolemia (PMID: 16250003, 18325082). This variant has been identified in 1/251448 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.
All of Us Research Program, National Institutes of Health RCV000237637 SCV004825977 uncertain significance Hypercholesterolemia, familial, 1 2023-09-18 criteria provided, single submitter clinical testing This missense variant (also known as p.Val815Ile in the mature protein) replaces valine with isoleucine at codon 836 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 at least one individual affected with familial hypercholesterolemia (PMID: 16250003, 18325082). This variant has been identified in 1/251448 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.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237637 SCV000606664 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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