ClinVar Miner

Submissions for variant NM_000282.4(PCCA):c.437T>C (p.Leu146Pro) (rs774457925)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186079 SCV000239103 likely pathogenic not provided 2014-01-30 criteria provided, single submitter clinical testing p.Leu146Pro (CTT>CCT): c.437 T>C in exon 6 of the PCCA gene (NM_000282.3) The L146P missense change in the PCCA gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The L146P variant is a semi-conservative amino acid substitution as these residues share similar properties, but differ in size, charge, or other properties which may impact secondary structure. This substitution occurs at a highly conserved position in the PCCA protein, and multiple in-silico analysis programs predict that L146P is damaging to the PCCA protein. Therefore, L146P is a strong candidate for a disease-causing mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in UCD-MET panel(s).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193473 SCV001362338 uncertain significance not specified 2020-11-10 criteria provided, single submitter clinical testing Variant summary: PCCA c.437T>C (p.Leu146Pro) results in a non-conservative amino acid change located in the Biotin carboxylase-like, N-terminal domain (IPR005481) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251170 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.437T>C in individuals affected with Propionic Acidemia and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.

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