Submissions for variant NM_000527.5(LDLR):c.910G>T (p.Asp304Tyr)

dbSNP: rs121908030

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel	RCV000237933	SCV001960919	likely pathogenic	Hypercholesterolemia, familial, 1	2021-06-08	reviewed by expert panel	curation	The NM_000527.5(LDLR):c.910G>T (p.Asp304Tyr) variant is classified as Likely pathogenic for Familial Hypercholesterolemia by applying evidence codes (PM5_Strong, PM2, PP3 and PP4) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: PM5_strong - Four more missense variants described in same codon, of which 2 variants classified as Pathogenic, so PM5_Strong is Met. PM2 - No population data was found for this variant in gnomAD (gnomAD v2.1.1). PP3 - REVEL = 0.982. PP4 - Variant meets PM2. Identified in 1 FH case who fulfills Simon-Broome criteria for FH in PMID 1301940.
LDLR-LOVD, British Heart Foundation	RCV000237933	SCV000295046	likely pathogenic	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix	RCV000237933	SCV000503250	pathogenic	Hypercholesterolemia, familial, 1	2016-12-16	criteria provided, single submitter	clinical testing	subjects mutated among 2600 FH index cases screened = 2 , family members = 2 with co-segregation / previously described in association with FH / Software predictions: Damaging
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille	RCV000237933	SCV000583758	pathogenic	Hypercholesterolemia, familial, 1	2017-03-30	criteria provided, single submitter	clinical testing