ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1792A>C (p.Ile598Leu)

dbSNP: rs879255023
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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 RCV000237670 SCV004022462 uncertain significance Hypercholesterolemia, familial, 1 2023-04-28 reviewed by expert panel curation The NM_000527.5(LDLR):c.1792A>C (p.Ile598Leu) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2, PP4 and BP4) 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). PP4 - Variant meet PM2. PMID: 11810272 (Fouchier et al., 2001), Netherlands - et least 1 case who fulfills validated clinical criteria for FH. BP4 - REVEL: 0.487, it is below 0.50, splicing evaluation required. Functional data on splicing not available. Scenario A, Acceptor site: The variant is not located at -20 to +3 bases of canonical acceptor splicing site of any exons. Scenario A, Donor site: The variant is not located at -3 to +6 bases of canonical splicing site of any exons. Scenario B, Acceptor site: The variant is located within the range but does not create de novo AG site. Scenario B, Donor site: The variant is located within range but does not create de novo GT site. Scenario C, Acceptor site: The variant is located at -20 to +3 bases of intraexonic AG but AG is not within the range. Scenario C, Donor site: The variant is not located at -3 to +6 bases of intraexonic GT Interpretation: The variant does not affect splicing.
LDLR-LOVD, British Heart Foundation RCV000237670 SCV000295659 likely benign Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237670 SCV000606516 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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