ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.514G>T (p.Asp172Tyr)

dbSNP: rs879254554
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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 RCV000238056 SCV000294758 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge RCV000238056 SCV000599334 pathogenic Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter curation
Brunham Lab, Centre for Heart and Lung Innovation, University of British Columbia RCV000238056 SCV001432609 pathogenic Hypercholesterolemia, familial, 1 2019-06-04 criteria provided, single submitter research
Invitae RCV002519841 SCV003443867 likely pathogenic Familial hypercholesterolemia 2022-11-29 criteria provided, single submitter clinical testing This variant is also known as D151Y. This missense change has been observed in individual(s) with hypercholesterolemia (PMID: 11194025). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 172 of the LDLR protein (p.Asp172Tyr). ClinVar contains an entry for this variant (Variation ID: 251268). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Asp172 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10532689, 16806138, 25545329). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects LDLR function (PMID: 20599862). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt LDLR protein function.

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