ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.514G>C (p.Asp172His)

dbSNP: rs879254554
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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 RCV000237481 SCV000294757 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Invitae RCV003581601 SCV004298321 pathogenic Familial hypercholesterolemia 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 172 of the LDLR protein (p.Asp172His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with familial hypercholesterolemia (PMID: 10882754, 33732287). This variant is also known as D151H. ClinVar contains an entry for this variant (Variation ID: 251267). 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 with a positive predictive value of 95%. 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. For these reasons, this variant has been classified as Pathogenic.
Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences RCV000237481 SCV001467721 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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