ClinVar Miner

Submissions for variant NM_024649.5(BBS1):c.1535G>A (p.Arg512His) (rs202205304)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000490348 SCV000267221 uncertain significance Bardet-Biedl syndrome 1 2016-03-18 criteria provided, single submitter reference population
Counsyl RCV000490348 SCV000796843 uncertain significance Bardet-Biedl syndrome 1 2018-01-02 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000825288 SCV000966582 uncertain significance not specified 2018-07-18 criteria provided, single submitter clinical testing The p.Arg512His variant in BBS1 has been reported in the heterozygous state in 1 individual with Bardet-Biedl syndrome (BBS) who also carried 2 other reportedly damaging alleles in another gene known to cause BBS (Chen 2011). This variant h as also been reported in ClinVar (Variation ID: 225300). This variant has been i dentified in 0.01% (13/126704) of European chromosomes by the Genome Aggregation Database (gnomAD,; dbSNP rs202205304). Althoug h this variant has been seen in the general population, its frequency is low eno ugh to be consistent with a recessive carrier frequency. Computational predictio n tools and conservation analysis suggest that the ${MatchVariant_1_AminoAcidCha nge} variant may not impact the protein, though this information is not predicti ve enough to rule out pathogenicity. In summary, the clinical significance of th is variant is uncertain. ACMG/AMP Criteria applied: PM2_Supporting.
Invitae RCV001048535 SCV001212547 uncertain significance Bardet-Biedl syndrome 2019-12-02 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 512 of the BBS1 protein (p.Arg512His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs202205304, ExAC 0.02%). This variant has not been reported in the literature in individuals with BBS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 225300). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Illumina Clinical Services Laboratory,Illumina RCV000490348 SCV001264353 uncertain significance Bardet-Biedl syndrome 1 2017-10-13 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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