Submissions for variant NM_006343.3(MERTK):c.2189+1G>T

gnomAD frequency: 0.00004  dbSNP: rs371956016

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000624145	SCV000741690	pathogenic	Inborn genetic diseases	2016-08-10	criteria provided, single submitter	clinical testing
Mendelics	RCV000005734	SCV001135928	pathogenic	Retinitis pigmentosa 38	2019-05-28	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001073654	SCV001239205	pathogenic	Retinal dystrophy	2019-08-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001208965	SCV001380383	pathogenic	not provided	2024-01-15	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 16 of the MERTK 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 MERTK are known to be pathogenic (PMID: 24265693, 29659094). This variant is present in population databases (rs371956016, gnomAD 0.005%). Disruption of this splice site has been observed in individual(s) with cone-rod dystrophy (PMID: 17301963). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 5403). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001208965	SCV002762216	pathogenic	not provided	2022-06-09	criteria provided, single submitter	clinical testing	Canonical splice site variant demonstrated to result in a null allele in a gene for which loss of function is a known mechanism of disease (Ebermann I et al., 2007; This variant is associated with the following publications: (PMID: 25525159, 31589614, 17301963, 31370859, 32552793)
Ophthalmic Genetics Group, Institute of Molecular and Clinical Ophthalmology Basel	RCV003324483	SCV004030421	pathogenic	Retinitis pigmentosa	2023-07-24	criteria provided, single submitter	research	Clinical significance based on ACMG v2.0
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000005734	SCV004805925	pathogenic	Retinitis pigmentosa 38	2024-03-25	criteria provided, single submitter	clinical testing
OMIM	RCV000005734	SCV000025916	pathogenic	Retinitis pigmentosa 38	2007-06-01	no assertion criteria provided	literature only
Faculty of Health Sciences, Beirut Arab University	RCV001257903	SCV001434671	pathogenic	Autosomal recessive retinitis pigmentosa	2015-09-10	no assertion criteria provided	literature only