Submissions for variant NM_000527.5(LDLR):c.1211C>T (p.Thr404Ile)

dbSNP: rs879254835

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel	RCV000237211	SCV005688670	likely pathogenic	Hypercholesterolemia, familial, 1	2022-10-28	reviewed by expert panel	curation	The NM_000527.5(LDLR):c.1211C>T (p.Thr404Ile) variant is classified as Likely Pathogenic for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PM3, PP3, PP4 and PS4_Supporting as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 28 October 2022. The supporting evidence is as follows: PM2: This variant is absent from gnomAD v2.1.1. PP3: REVEL = 0.928. PS4_Supporting, PP4: Variant meets PM2 and is identified in at least 2 unrelated index cases who fulfill criteria for FH after alternative causes of high cholesterol were excluded (1 case with DLCN score >=6 from Research Lab of Molecular Genetics of Lipid Metabolism - Prof. M.Arca, Italy; 1 case from PMID 19446849). PM3: Variant meets PM2 and is identified in an index case with homozygous FH phenotype and LDLR variant (c.428G>A (p.Cys143Tyr)) classified as Pathogenic by these guidelines, in trans (PMID 14570618, 19073363).
LDLR-LOVD, British Heart Foundation	RCV000237211	SCV000295302	likely pathogenic	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000237211	SCV000599367	pathogenic	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	curation
Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II	RCV000237211	SCV001653627	likely pathogenic	Hypercholesterolemia, familial, 1	2021-05-24	criteria provided, single submitter	clinical testing