ClinVar Miner

Submissions for variant NM_000071.2(CBS):c.1316G>A (p.Arg439Gln) (rs756467921)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169494 SCV000220951 likely benign Homocystinuria due to CBS deficiency 2014-12-16 criteria provided, single submitter literature only
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000587586 SCV000331007 uncertain significance not provided 2015-11-19 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587586 SCV000695303 uncertain significance not provided 2016-03-04 criteria provided, single submitter clinical testing
Invitae RCV000169494 SCV000543514 uncertain significance Homocystinuria due to CBS deficiency 2017-04-13 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 439 of the CBS protein (p.Arg439Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs756467921, ExAC 0.03%). This variant has been reported to co-occur in cis with another likely pathogenic variant (p.Glu144Lys) in three individuals affected with homocystinuria (PMID: 9156316, 12124992). There is also evidence that this variant co-occurs in trans with other pathogenic variants in individuals with homocystinuria (PMID: 10462600, 12124992).  ClinVar contains an entry for this variant (Variation ID: 189088). Experimental studies have shown that this missense change does not have a substantial impact on protein function (PMID: 9156316, 22267502, 22069143, 20506325, 20490928). In summary, this variant is a rare missense change that is present in the general population and it has been reported in individuals affected with homocystinuria. However experimental studies have shown that it does not affect protein function. It has been classified as a Variant of Uncertain Significance.

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