ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.253G>A (p.Gly85Arg) (rs863223435)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000195506 SCV000249722 pathogenic not provided 2018-09-07 criteria provided, single submitter clinical testing The G85R pathogenic variant in the CBS gene has been reported previously either in the homozygous state or with another CBS pathogenic variant in multiple individuals with homocystinuria (Maclean et al., 2002; De Lucca et al, 2004; Cozar et al, 2011; Casique et al., 2013; Karaca et al., 2014). Functional studies in E. coli demonstrated that the G85R variant was associated with no detectable CBS enzyme activity (Maclean et al., 2002). The G85R 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 G85R variant is a non-conservative amino acid substitution and occurs at a position that is conserved across species. We interpret G85R as a pathogenic variant.
Invitae RCV001063052 SCV001227885 pathogenic Classic homocystinuria 2019-12-19 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 85 of the CBS protein (p.Gly85Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with homocystinuria (PMID: 21520339, 23981774, 12007221, 29352562, 14972327, 24211323). ClinVar contains an entry for this variant (Variation ID: 212874). This variant has been reported to affect CBS protein function (PMID: 12007221, 22267502). For these reasons, this variant has been classified as Pathogenic.

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