Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000169515 | SCV000220985 | likely pathogenic | Bardet-Biedl syndrome | 2014-12-23 | criteria provided, single submitter | literature only | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000169515 | SCV000918635 | likely pathogenic | Bardet-Biedl syndrome | 2018-08-06 | criteria provided, single submitter | clinical testing | Variant summary: BBS1 c.1131_1135delCTTTG (p.Cys377TrpfsX36) 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. One truncation downstream of this position has been classified as pathogenic by our laboratory (c.1645G>T, p.Glu549X). The variant allele was found at a frequency of 8.1e-06 in 246256 control chromosomes (gnomAD). The variant, c.1131_1135delCTTTG, has been reported in the literature in an individual affected with Bardet-Biedl Syndrome (Mykytyn_2003) but also in patients with non-syndromic retinitis pigmentosa and Leber congenital amaurosis (Estrada-Cuzcano_2012, Haer-Wigman_2017). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Gene |
RCV001008111 | SCV001167861 | pathogenic | not provided | 2018-06-08 | criteria provided, single submitter | clinical testing | The c.1131_1135delCTTTG variant in the BBS1 gene has been reported previously using alternate nomenclature (c.1130_1134del) in association with autosomal recessive Bardet-Biedl syndrome (Mykytyn et al., 2003; Estrada-Cuzcano et al., 2012). The c.1131_1135delCTTTG variant causes a frameshift starting with codon Cysteine 377, changes this amino acid to a Tryptophan residue, and creates a premature Stop codon at position 36 of the new reading frame, denoted p.Cys377TrpfsX36. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1131_1135delCTTTG variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.1131_1135delCTTTG as a pathogenic variant. |
Invitae | RCV000169515 | SCV004294876 | pathogenic | Bardet-Biedl syndrome | 2023-09-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Cys377Trpfs*36) 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 (rs786204701, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with clinical features of Bardet-Biedl syndrome (PMID: 12524598, 23143442). This variant is also known as c.1130_1134del. ClinVar contains an entry for this variant (Variation ID: 189103). For these reasons, this variant has been classified as Pathogenic. |