Submissions for variant NM_000527.5(LDLR):c.2416del (p.Val806fs)

dbSNP: rs773618064

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
LDLR-LOVD, British Heart Foundation	RCV000237939	SCV000296000	pathogenic	Hypercholesterolemia, familial, 1	2016-03-25	criteria provided, single submitter	literature only
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille	RCV000237939	SCV000583951	pathogenic	Hypercholesterolemia, familial, 1	2017-03-30	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001854911	SCV002113948	pathogenic	Familial hypercholesterolemia	2021-08-27	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the LDLR protein in which other variant(s) (p.Ser849*) have been determined to be pathogenic (PMID: 11933210, 26892515). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 252329). This variant is also known as c.2412delG, p.L804fs, c.2416_2418delG, FsV785. This frameshift has been observed in individual(s) with familial hypercholesterolemia (PMID: 16542394, 20809525). This variant is not present in population databases (ExAC no frequency). This sequence change results in a frameshift in the LDLR gene (p.Val806Serfs*123). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 55 amino acid(s) of the LDLR protein and extend the protein by 67 additional amino acid residues.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000237939	SCV005374104	pathogenic	Hypercholesterolemia, familial, 1	2024-09-22	criteria provided, single submitter	clinical testing