Submissions for variant NM_000527.5(LDLR):c.1907G>T (p.Gly636Val)

dbSNP: rs879255072

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel	RCV000505212	SCV002817125	uncertain significance	Hypercholesterolemia, familial, 1	2022-08-29	reviewed by expert panel	curation	The NM_000527.5(LDLR):c.1907G>T (p.Gly636Val) 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/10.1101/2021.03.17.21252755). The supporting evidence is as follows: PM2 - This variant is absent from gnomAD (gnomAD v2.1.1), so PM2 is Met. PP3 - REVEL = 0.977. It is above 0.75, so PP3 is Met. PP4 - Variant meets PM2 and is identified in 1 index case who fulfills SB criteria for FH [(1) for adults, TC>7.8 mmol/L or LDL>.4.4 mmol/L; (2) for children <16 years old, TC>6.7 mmol/L; (3) patients or their relatives have tendon xanthomas; (4) patients with xanthomas whose TC > 16 mmol/L are diagnosed as homozygous and the others patients are diagnosed as heterozygous] from China (PMID: 24671153), so PP4 is Met.
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000505212	SCV000599399	likely pathogenic	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	curation