Submissions for variant NM_025114.4(CEP290):c.180+1G>A (rs758593134)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000542843	SCV000634642	pathogenic	Joubert syndrome; Meckel-Gruber syndrome; Nephronophthisis	2019-12-04	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 3 of the CEP290 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs758593134, ExAC 0.003%). Disruption of this splice site has been observed in individuals with Leber congenital amaurosis (PMID: 16909394, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115). For these reasons, this variant has been classified as Pathogenic.
Molecular Genetics Laboratory,Institute for Ophthalmic Research	RCV001199655	SCV001162443	pathogenic	Retinitis pigmentosa	2020-01-09	criteria provided, single submitter	research
CeGaT Praxis fuer Humangenetik Tuebingen	RCV001091342	SCV001247310	pathogenic	not provided	2018-02-01	criteria provided, single submitter	clinical testing
Medical Genetics Laboratory, Kennedy Center,Juliane Marie Center, Rigshospitalet	RCV000787558	SCV000926534	likely pathogenic	Leber congenital amaurosis	2018-04-01	no assertion criteria provided	research