ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.967G>T (p.Gly323Cys)

dbSNP: rs373869746
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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 RCV000417282 SCV002568018 likely pathogenic Hypercholesterolemia, familial, 1 2022-08-28 reviewed by expert panel curation The NM_000527.5(LDLR):c.967G>T (p.Gly323Cys) variant is classified as Likely pathogenic for Familial Hypercholesterolemia by applying evidence codes PM2, PP1, PP3, PS4_Supporting and PP4 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), so PM2 is met. PP1 - variant segregates with the FH phenotype in 2 informative meiosis (1 from each family) from Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies (APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière): 2 relatives with LDL>75th percentile have the variant, so PP1 is met. PP3 - REVEL = 0.903. It is above 0.75, so PP3 is met. PS4_supporting - variant meets PM2 and was identified in 4 unrelated index cases who fulfill at least SB Possible criteria for FH from Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies (APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière), so PS4_Supporting is met PP4 - variant meets PM2 and was identified in 4 unrelated index cases who fulfill clinical criteria for FH after alternative causes for high cholesterol were excluded (please see PS4 for details), so PP4 is met.
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000417282 SCV000503270 pathogenic Hypercholesterolemia, familial, 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 3 , family member = 1 with co-segregation / other mutation at same codon / Software predictions: Damaging
Mayo Clinic Laboratories, Mayo Clinic RCV004791443 SCV005413310 likely pathogenic not provided 2024-06-25 criteria provided, single submitter clinical testing PP1, PP3, PP4, PM2, PS4_supporting

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