ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.2320G>A (p.Asp774Asn) (rs138190838)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics Laboratory,Centre for Cardiovascular Surgery and Transplantation RCV000454979 SCV000540904 uncertain significance Familial hypercholesterolemia 1 2017-03-27 criteria provided, single submitter clinical testing
Color Health, Inc RCV001178333 SCV001342739 likely benign Familial hypercholesterolemia 2019-01-31 criteria provided, single submitter clinical testing
Invitae RCV001178333 SCV001537983 uncertain significance Familial hypercholesterolemia 2020-08-20 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 774 of the LDLR protein (p.Asp774Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs138190838, ExAC 0.06%). This variant has been observed in individual(s) with elevated low-density lipoprotein (LDL) cholesterol and/or premature myocardial infarction (PMID: 24507775, 30971288). ClinVar contains an entry for this variant (Variation ID: 403663). 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 asparagine 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.

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