ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1154T>C (p.Leu385Pro)

dbSNP: rs879254809
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel RCV000508767 SCV004022441 uncertain significance Hypercholesterolemia, familial, 1 2023-04-28 reviewed by expert panel curation The NM_000527.5(LDLR):c.1154T>C (p.Leu385Pro) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2 and PP3) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v2.1.1). PP3: REVEL = 0.787.
Ambry Genetics RCV002358394 SCV002620124 uncertain significance Cardiovascular phenotype 2020-08-05 criteria provided, single submitter clinical testing The p.L385P variant (also known as c.1154T>C), located in coding exon 8 of the LDLR gene, results from a T to C substitution at nucleotide position 1154. The leucine at codon 385 is replaced by proline, an amino acid with similar properties, and is located in an EGF-like domain. Other variants affecting this codon (p.L385R, c.1154T>G and p.L385V, c.1153C>G) have been detected in hypercholesterolemia cohorts (Kotze MJ et al. Clin. Genet., 1998 Jul;54:74-8; Marduel M et al. Hum. Mutat., 2010 Nov;31:E1811-24). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000508767 SCV000606338 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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