ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1438G>A (p.Ala480Thr)

dbSNP: rs879254901
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001857284 SCV002265144 likely pathogenic Familial hypercholesterolemia 2022-11-29 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 480 of the LDLR protein (p.Ala480Thr). 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.Ala480 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18701038, 27830735; Invitae). 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. ClinVar contains an entry for this variant (Variation ID: 440644). This missense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 26802169). This variant is not present in population databases (gnomAD no frequency).
GeneDx RCV003317248 SCV004021824 likely pathogenic not provided 2023-01-04 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as p.A459T; This variant is associated with the following publications: (PMID: 26802169)
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000508781 SCV000606427 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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