ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.689del (p.Leu230fs) (rs775351239)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169175 SCV000220407 likely pathogenic Homocystinuria due to CBS deficiency 2014-06-11 criteria provided, single submitter literature only
GeneDx RCV000198642 SCV000249735 pathogenic not provided 2015-02-06 criteria provided, single submitter clinical testing The c.689delT mutation in the CBS gene has been reported as homozygous in one Argentinian individual with a severe clinical presentation of homocystinuria, and was absent from 100 Spanish control chromosomes (Cozar et al., 2011). This mutation causes a shift in reading frame starting at codon Leucine 230, changing it to an Arginine, and creating a premature stop codon at position 39 of the new reading frame, denoted p.Leu230ArgfsX39. This mutation is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Other frameshift mutations in the CBS gene have been reported in association with homocystinuria. In summary, c.689delT in the CBS gene is interpreted as a disease-causing mutation.
Invitae RCV000169175 SCV000935887 pathogenic Homocystinuria due to CBS deficiency 2018-11-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu230Argfs*39) in the CBS gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs775351239, ExAC 0.001%). This variant has been observed as homozygous in an individual affected with homocystinuria (PMID: 21520339). ClinVar contains an entry for this variant (Variation ID: 188829). Loss-of-function variants in CBS are known to be pathogenic (PMID: 10338090, 12124992). For these reasons, this variant has been classified as Pathogenic.

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