ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.434T>C (p.Val145Ala)

gnomAD frequency: 0.00004  dbSNP: rs776872913
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000238382 SCV000294709 likely benign Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Color Diagnostics, LLC DBA Color Health RCV001526129 SCV001736422 uncertain significance Familial hypercholesterolemia 2023-02-01 criteria provided, single submitter clinical testing This missense variant (also known as p.Val124Ala in the mature protein) replaces valine with alanine at codon 145 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in six individuals showing LDL-C levels not significantly higher than control individuals (Hartgers 2020 dissertation, Univ. Amsterdam). This variant has been identified in 5/282590 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Although there is no indication this variant causes disease, additional studies are necessary 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 RCV000238382 SCV004820170 uncertain significance Hypercholesterolemia, familial, 1 2023-06-15 criteria provided, single submitter clinical testing This missense variant (also known as p.Val124Ala in the mature protein) replaces valine with alanine at codon 145 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). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in six individuals showing LDL-C levels not significantly higher than control individuals (Hartgers 2020 dissertation, Univ. Amsterdam). This variant has been identified in 5/282590 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Although there is no indication this variant causes disease, additional studies are necessary 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 RCV000238382 SCV000606119 benign Hypercholesterolemia, familial, 1 no assertion criteria provided research

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