Submissions for variant NM_025114.4(CEP290):c.829G>T (p.Glu277Ter)

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Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001004996	SCV001164554	likely pathogenic	Leber congenital amaurosis 10	2018-12-03	criteria provided, single submitter	research	The heterozygous p.Glu277Ter variant in CEP290 was identified by our study in the compound heterozygous state, with a VUS, in one individual with Leber congenital amaurosis. The p.Glu277Ter variant in CEP290 has not been previously reported in individuals with Leber congenital amaurosis and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 277, which is predicted to lead to a truncated or absent protein. Loss of function of the CEP290 gene is an established disease mechanism in autosomal recessive Leber congenital amaurosis. In summary, although additional studies are required to fully establish its clinical significance, the clinial significance of this variant is likely pathogenic. Criteria applied: PM2, PVS1 (Richards 2015).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001860572	SCV002237201	pathogenic	Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis	2021-09-15	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 813995). This variant has not been reported in the literature in individuals affected with CEP290-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu277*) in the CEP290 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115).
Fulgent Genetics, Fulgent Genetics	RCV002479201	SCV002802884	likely pathogenic	Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14	2021-11-06	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003467577	SCV004216543	pathogenic	Bardet-Biedl syndrome 14	2023-11-23	criteria provided, single submitter	clinical testing

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