Submissions for variant NM_000527.5(LDLR):c.1449G>T (p.Trp483Cys)

dbSNP: rs879254907

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel	RCV000237631	SCV004022408	uncertain significance	Hypercholesterolemia, familial, 1	2023-04-28	reviewed by expert panel	curation	The NM_000527.5(LDLR):c.1449G>T (p.Trp483Cys) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2, PP3, 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. PP3 - REVEL = 0.951. It is above 0.75, so PP3 is Met. PP4 - Variant meets PM2 and is identified in 1 index case with Simon Broome criteria from Poland (PMID 26892515), after alternative causes of high cholesterol were excluded.
LDLR-LOVD, British Heart Foundation	RCV000237631	SCV000295441	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum	RCV000237631	SCV000606433	pathogenic	Hypercholesterolemia, familial, 1		no assertion criteria provided	research