ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.679G>A (p.Asp227Asn)

dbSNP: rs2077282480
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001056153 SCV001220576 likely pathogenic Familial hypercholesterolemia 2022-11-29 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 851708). 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.Asp227 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 2352257, 2569482, 17539906, 19467224, 21310417, 21382890, 22883975, 23375686, 23669246, 27680772). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This missense change has been observed in individual(s) with clinical features of familial hypercholesterolemia (PMID: 31491741). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 227 of the LDLR protein (p.Asp227Asn).

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