ClinVar Miner

Submissions for variant NM_000532.5(PCCB):c.1283C>T (p.Thr428Ile) (rs111033542)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000012796 SCV000798999 pathogenic Propionyl-CoA carboxylase deficiency 2018-04-02 criteria provided, single submitter clinical testing
GeneReviews RCV000012796 SCV000055679 pathologic Propionyl-CoA carboxylase deficiency 2012-05-17 no assertion criteria provided curation Converted during submission to Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000012796 SCV000697268 pathogenic Propionyl-CoA carboxylase deficiency 2016-07-08 criteria provided, single submitter clinical testing Variant summary: The c.1283C>T (p.Tre428Ile) in PCCB gene is a missense change that alters a highly conserved nucleotide and 5/5 in silico tools predict deleterious outcome. The variant falls into the carboxyl-terminal portion of the b-subunit and mutations in this region are likely to diminish the ability of the mutant bPCC proteins to form PCC active oligomers. These predictions were also confirmed by functional studies, where no detectable enzymatic activities were found in fibroblasts of a patient homozygous T428I. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.00002 (3/121052 chrs tested). This frequency does not exceed the maximal expected allele frequency for a pathogenic variant in PCCB gene (0.0025). The variant was found in multiple affected individuals with established dx of propionic acidemia. Kim (2002) and Ohura (1993) report the frequency of the variant of interest in affected individuals as 56.3% and 50%, respectively. Lastly, a reputable database/diagnostic center classified the variant of interest as Pathogenic. Taken together, the variant was classified as Pathogenic.
OMIM RCV000012796 SCV000033036 pathogenic Propionyl-CoA carboxylase deficiency 1993-01-01 no assertion criteria provided literature only

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