ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.676T>C (p.Ser226Pro)

dbSNP: rs879254635
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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 RCV000237302 SCV000294894 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Molecular Genetics Laboratory, Centre for Cardiovascular Surgery and Transplantation RCV000237302 SCV000540750 likely pathogenic Hypercholesterolemia, familial, 1 2016-11-05 criteria provided, single submitter clinical testing Disrupt SDE motif. SDE bind structural Ca2+.
Fundacion Hipercolesterolemia Familiar RCV000237302 SCV000607490 pathogenic Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV005090216 SCV005837080 pathogenic Familial hypercholesterolemia 2024-09-11 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 226 of the LDLR protein (p.Ser226Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant familial hypercholesterolemia (PMID: 1301956, 11139254, 11668640; internal data). This variant is also known as FH Miami-1, S205P. ClinVar contains an entry for this variant (Variation ID: 251384). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt LDLR protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

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