Submissions for variant NM_000527.5(LDLR):c.514G>A (p.Asp172Asn) (rs879254554)

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
LDLR-LOVD, British Heart Foundation	RCV000238587	SCV000294756	likely pathogenic	Familial hypercholesterolemia 1	2016-03-25	criteria provided, single submitter	literature only
Robarts Research Institute,Western University	RCV000238587	SCV000484687	likely pathogenic	Familial hypercholesterolemia 1		criteria provided, single submitter	clinical testing
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix	RCV000238587	SCV000503172	likely pathogenic	Familial hypercholesterolemia 1	2016-12-16	criteria provided, single submitter	clinical testing	subjects mutated among 2600 FH index cases screened = 2 / Software predictions: Conflicting
Fundacion Hipercolesterolemia Familiar	RCV000238587	SCV000607467	pathogenic	Familial hypercholesterolemia 1	2016-03-01	criteria provided, single submitter	research
Invitae	RCV001385842	SCV001585835	pathogenic	Familial hypercholesterolemia	2020-10-28	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid with asparagine at codon 172 of the LDLR protein (p.Asp172Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with familial hypercholesterolemia (PMID: 10532689, 16806138). It has also been observed to segregate with disease in related individuals. This variant is also known as D151N. ClinVar contains an entry for this variant (Variation ID: 251266). Experimental studies have shown that this variant affects LDLR protein function (PMID: 25545329). This variant disrupts the p.Asp172 (also known as D151) amino acid residue in LDLR. Other variant(s) that disrupt this residue have been observed in individuals with LDLR-related conditions (PMID: 10882754, 11194025, 20538126, 28028493), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II	RCV000238587	SCV001653595	likely pathogenic	Familial hypercholesterolemia 1	2021-05-24	criteria provided, single submitter	clinical testing	Reduced binding activity & LDL uptake versus WT
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum	RCV000238587	SCV000606142	pathogenic	Familial hypercholesterolemia 1		no assertion criteria provided	research