ClinVar Miner

Submissions for variant NM_024649.5(BBS1):c.734C>T (p.Pro245Leu)

gnomAD frequency: 0.00031  dbSNP: rs151203205
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001246356 SCV001419703 uncertain significance Bardet-Biedl syndrome 2022-08-15 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 245 of the BBS1 protein (p.Pro245Leu). This variant is present in population databases (rs151203205, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with BBS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 970728). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV001835263 SCV002781959 uncertain significance Bardet-Biedl syndrome 1 2022-05-31 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003938576 SCV004756142 uncertain significance BBS1-related condition 2023-11-27 criteria provided, single submitter clinical testing The BBS1 c.734C>T variant is predicted to result in the amino acid substitution p.Pro245Leu. This variant was previously reported in the heterozygous state in one individual with Bardet-Biedl syndrome; a second causative variant was not detected in the same gene (Janssen et al. 2011. PubMed ID: 21052717). In a second study, this variant was found along with a second variant in MKS1 in a patient presenting with non-obese juvenile-onset diabetes, learning difficulties, speech delay, short stature, and brachydactyly (Dallali et al. 2021. PubMed ID: 34691137). Dallali et al. suggest a possible oligogenic inheritance pattern for Bardet-Biedl syndrome. This variant is reported in 0.10% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-66288751-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Natera, Inc. RCV001835263 SCV002094739 uncertain significance Bardet-Biedl syndrome 1 2020-03-21 no assertion criteria provided clinical testing

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