Submissions for variant NM_000527.5(LDLR):c.1120_1123dup (p.Tyr375fs)

dbSNP: rs879254799

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
LDLR-LOVD, British Heart Foundation	RCV000237857	SCV000295232	pathogenic	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix	RCV000237857	SCV000503301	pathogenic	Hypercholesterolemia, familial, 1	2016-12-16	criteria provided, single submitter	clinical testing	subjects mutated among 2600 FH index cases screened = 3 / previously described in association with FH
Invitae	RCV000792875	SCV000932200	pathogenic	Familial hypercholesterolemia	2023-08-17	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr375Trpfs*7) in the LDLR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with familial hypercholesterolemia (PMID: 10660340, 23375686). This variant is also known as c.1119_1122dupTGGC. ClinVar contains an entry for this variant (Variation ID: 251676). For these reasons, this variant has been classified as Pathogenic.
Laboratory of molecular diagnosis of dyslipidemias, Università egli studi di Napoli Federico II	RCV000237857	SCV001653622	pathogenic	Hypercholesterolemia, familial, 1	2021-05-24	criteria provided, single submitter	clinical testing