ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.656G>A (p.Gly219Asp) (rs201384282)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Dept. of Genetics and Pharmacogenomics, Merck Research Labs RCV000162018 SCV000189621 not provided not provided no assertion provided in vitro
Invitae RCV000819529 SCV000960194 uncertain significance Familial hypercholesterolemias 2018-09-17 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 219 of the LDLR protein (p.Gly219Asp). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs201384282, ExAC 0.003%). This variant has been reported in an individual affected with hypercholesterolemia (PMID: 9678702, 15135252). This variant is also known as G198D in the literature. ClinVar contains an entry for this variant (Variation ID: 183137). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
LDLR-LOVD, British Heart Foundation RCV000238334 SCV000294856 likely benign Familial hypercholesterolemia 2016-03-25 criteria provided, single submitter literature only

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