ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1637G>T (p.Gly546Val)

dbSNP: rs28942081
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237102 SCV000295552 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Iberoamerican FH Network RCV000237102 SCV000748057 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research
Invitae RCV001854904 SCV002228783 pathogenic Familial hypercholesterolemia 2022-07-19 criteria provided, single submitter clinical testing This variant disrupts the p.Gly546 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17539906, 22859806; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 251947). This variant is also known as p.G525V. This missense change has been observed in individuals with familial hypercholesterolemia (PMID: 15823280, 17539906, 21722902). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 546 of the LDLR protein (p.Gly546Val). For these reasons, this variant has been classified as Pathogenic.

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