ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.374G>A (p.Arg125Gln) (rs781444670)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000723426 SCV000230842 pathogenic not provided 2014-11-20 criteria provided, single submitter clinical testing
Invitae RCV000178709 SCV000649834 pathogenic Classic homocystinuria 2020-08-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 125 of the CBS protein (p.Arg125Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs781444670, ExAC 0.003%). This variant has been reported in numerous individuals affected with homocystinuria both in the homozygous and compound heterozygous state (PMID: 7849717, 9587029, 12124992, 10338090), with evidence of co-segregation with disease in one family (PMID: 21520339). ClinVar contains an entry for this variant (Variation ID: 197625). Experimental studies have shown that this missense change causes a deleterious effect on CBS protein structure and function (PMID: 7849717, 22612060, 20506325, 20308073). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000178709 SCV000791085 likely pathogenic Classic homocystinuria 2017-04-27 no assertion criteria provided clinical testing
Natera, Inc. RCV000178709 SCV001452098 pathogenic Classic homocystinuria 2020-09-16 no assertion criteria provided clinical testing
GenomeConnect - Invitae Patient Insights Network RCV000178709 SCV001749535 not provided Classic homocystinuria no assertion provided phenotyping only Variant interpreted as Pathogenic and reported on 12-05-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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