Submissions for variant NM_000527.5(LDLR):c.2100C>G (p.Asp700Glu)

dbSNP: rs759858813

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel	RCV000237946	SCV002506378	uncertain significance	Hypercholesterolemia, familial, 1	2022-03-25	reviewed by expert panel	curation	The NM_000527.5(LDLR):c.2100C>G (p.Asp700Glu) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2, 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. PS4_Supporting - Variant meets PM2 and is identified in 5 unrelated index cases who fulfill SB criteria for FH from Malaysia (PMID: 21418584), so PS4_Supporting is Met. PP4 - Variant meets PM2 and is identified in 5 unrelated index cases who fulfill clinical criteria for FH from several labs (see PS4 for details), so PP4 is Met.
LDLR-LOVD, British Heart Foundation	RCV000237946	SCV000295874	likely pathogenic	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
CeGaT Center for Human Genetics Tuebingen	RCV001090455	SCV001246012	pathogenic	not provided	2016-11-01	criteria provided, single submitter	clinical testing