ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2023G>A (p.Gly675Ser) (rs770744861)

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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 RCV000238136 SCV000295820 likely pathogenic Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Molecular Genetics Laboratory,Centre for Cardiovascular Surgery and Transplantation RCV000238136 SCV000540852 likely pathogenic Familial hypercholesterolemia 1 2016-11-05 criteria provided, single submitter clinical testing
Invitae RCV000810496 SCV000950699 uncertain significance Familial hypercholesterolemia 2019-10-25 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 675 of the LDLR protein (p.Gly675Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs770744861, ExAC 0.002%). This variant has been observed in individuals affected with familial hypercholesterolemia (PMID: 11754108, 27824480, 22698793). This variant is also known as p.Gly654Ser in the literature. ClinVar contains an entry for this variant (Variation ID: 252173). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Color Health, Inc RCV000810496 SCV001360361 uncertain significance Familial hypercholesterolemia 2018-12-05 criteria provided, single submitter clinical testing

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