ClinVar Miner

Submissions for variant NM_000071.3(CBS):c.65A>G (p.His22Arg)

gnomAD frequency: 0.00006  dbSNP: rs763151207
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197426 SCV000249717 uncertain significance not provided 2018-05-31 criteria provided, single submitter clinical testing The H22R variant in the CBS gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The H22R variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The H22R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant likely does not alter the protein structure/function. We interpret H22R as a variant of uncertain significance.
Invitae RCV002515348 SCV000769935 uncertain significance HYPERHOMOCYSTEINEMIA, THROMBOTIC, CBS-RELATED 2022-08-12 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 22 of the CBS protein (p.His22Arg). This variant is present in population databases (rs763151207, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CBS-related conditions. ClinVar contains an entry for this variant (Variation ID: 212870). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000197426 SCV002541703 uncertain significance not provided 2021-06-02 criteria provided, single submitter clinical testing
GenomeConnect-Association for Creatine Deficiencies, Association for Creatine Deficiencies RCV000648122 SCV001156347 not provided Classic homocystinuria no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 01-03-2018 by GTR ID 500031. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect facilitates ClinVar submission from the Association for Creatine Deficiencies registry and does not attempt to reinterpret the variant.
Natera, Inc. RCV000648122 SCV001452103 uncertain significance Classic homocystinuria 2020-09-16 no assertion criteria provided clinical testing

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