ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1886T>G (p.Phe629Cys)

gnomAD frequency: 0.00001  dbSNP: rs879255069
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237832 SCV000295742 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Invitae RCV001854908 SCV002298547 likely pathogenic Familial hypercholesterolemia 2022-11-29 criteria provided, single submitter clinical testing 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. 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: 252105). This missense change has been observed in individuals with familial hypercholesterolemia (PMID: 23375686; Invitae). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 629 of the LDLR protein (p.Phe629Cys).

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