Submissions for variant NM_024649.5(BBS1):c.1285C>T (p.Arg429Ter)

dbSNP: rs768443448

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169362	SCV000220733	likely pathogenic	Bardet-Biedl syndrome	2014-09-24	criteria provided, single submitter	literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000169362	SCV000699513	pathogenic	Bardet-Biedl syndrome	2021-05-10	criteria provided, single submitter	clinical testing	Variant summary: BBS1 c.1285C>T (p.Arg429X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 1.2e-05 in 251846 control chromosomes. c.1285C>T has been reported in the literature in individuals affected with Bardet-Biedl Syndrome and in at-least one individual among a cohort of patients with Leber congenital amaurosis (example, Beales_2003, Hichri_2005, Surl_2020, Hirano_2020). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (n=3)/likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae	RCV000169362	SCV000826045	pathogenic	Bardet-Biedl syndrome	2023-10-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg429*) in the BBS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS1 are known to be pathogenic (PMID: 12118255, 21520335, 27032803). This variant is present in population databases (rs768443448, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 12677556, 15770229, 20876674). ClinVar contains an entry for this variant (Variation ID: 188983). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000984149	SCV001150025	pathogenic	Bardet-Biedl syndrome 1	2018-01-25	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001092071	SCV001248425	pathogenic	not provided	2021-09-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000984149	SCV001520774	pathogenic	Bardet-Biedl syndrome 1	2024-03-23	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000984149	SCV001752721	pathogenic	Bardet-Biedl syndrome 1	2021-06-30	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000984149	SCV003824020	likely pathogenic	Bardet-Biedl syndrome 1	2022-03-22	criteria provided, single submitter	clinical testing
Counsyl	RCV000984149	SCV001132132	likely pathogenic	Bardet-Biedl syndrome 1	2014-09-24	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001092071	SCV001918628	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001092071	SCV001929003	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001092071	SCV001951708	pathogenic	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000984149	SCV002094764	pathogenic	Bardet-Biedl syndrome 1	2020-01-17	no assertion criteria provided	clinical testing