ClinVar Miner

Submissions for variant NM_000532.5(PCCB):c.1173dup (p.Val392fs) (rs587776758)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000012794 SCV000697265 pathogenic Propionyl-CoA carboxylase deficiency 2017-03-02 criteria provided, single submitter clinical testing Variant summary: The PCCB c.1173dupT (p.Val392Cysfs) variant results in a premature termination codon, predicted to cause a truncated or absent PCCB protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g.p.Gly407fs). One in silico tool predicts a damaging outcome for this variant. This variant is one of the most common pathogenic variant in Spanish patients with propionic acidemia and is absent in 121400 control chromosomes. Functional studies showed that the protein levels and PCC activity were extremely low in patients carrying this variant. Taken together, this variant is classified as pathogenic.
Invitae RCV000012794 SCV000961041 pathogenic Propionyl-CoA carboxylase deficiency 2018-10-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val392Cysfs*2) in the PCCB gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs753064211, ExAC 0.009%). This variant has been observed in several individuals affected with propionic acidemia (PMID: 9452096, 9683601, 20549364). ClinVar contains an entry for this variant (Variation ID: 12014). Loss-of-function variants in PCCB are known to be pathogenic (PMID: 15464417). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000012794 SCV000033034 pathogenic Propionyl-CoA carboxylase deficiency 1998-08-01 no assertion criteria provided literature only

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