ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1063A>G (p.Ile355Val)

gnomAD frequency: 0.00001  dbSNP: rs879254776
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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 RCV000237653 SCV000295194 likely benign Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Color Diagnostics, LLC DBA Color Health RCV001523919 SCV001733656 uncertain significance Familial hypercholesterolemia 2020-11-11 criteria provided, single submitter clinical testing This missense variant (also known as p.Ile334Val in the mature protein) replaces isoleucine with valine at codon 355 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 an individual affected with familial hypercholesterolemia (PMID: 10735632). This variant has been identified in 1/251216 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.
Invitae RCV001523919 SCV003442669 uncertain significance Familial hypercholesterolemia 2022-09-04 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). ClinVar contains an entry for this variant (Variation ID: 251642). This variant is also known as I334V. This missense change has been observed in individuals with clinical features of familial hypercholesterolemia (PMID: 10735632; Invitae). This variant is present in population databases (no rsID available, gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 355 of the LDLR protein (p.Ile355Val).
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237653 SCV000606313 benign Hypercholesterolemia, familial, 1 no assertion criteria provided research

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