Submissions for variant NM_015627.3(LDLRAP1):c.460-1G>A

dbSNP: rs2124688583

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001975710	SCV002254953	likely pathogenic	Hypercholesterolemia, familial, 4	2021-08-28	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has not been reported in the literature in individuals affected with LDLRAP1-related conditions. This sequence change affects an acceptor splice site in intron 4 of the LDLRAP1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LDLRAP1 are known to be pathogenic (PMID: 11326085, 12464675). This variant is not present in population databases (ExAC no frequency).
Institute of Human Genetics, University Hospital Muenster	RCV004584455	SCV002577958	pathogenic	See cases	2022-01-20	criteria provided, single submitter	clinical testing	ACMG categories: PVS1,PM2,PP3
Genome-Nilou Lab	RCV001975710	SCV004174039	pathogenic	Hypercholesterolemia, familial, 4	2023-04-11	criteria provided, single submitter	clinical testing