Submissions for variant NM_000282.4(PCCA):c.440del (p.Leu146_Ser147insTer)

dbSNP: rs1555361758

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000674020	SCV000799289	likely pathogenic	Propionic acidemia	2018-04-09	criteria provided, single submitter	clinical testing
GeneDx	RCV003117480	SCV003798668	pathogenic	not provided	2022-08-03	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 11592820, 10780784)
Baylor Genetics	RCV000674020	SCV004202900	pathogenic	Propionic acidemia	2022-10-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000674020	SCV004222737	pathogenic	Propionic acidemia	2023-11-16	criteria provided, single submitter	clinical testing	Variant summary: PCCA c.440delC (p.Ser147X) results in a premature termination codon and is predicted to cause absence of the protein due to nonsense mediated decay, a commonly known mechanism for disease. The variant was absent in 251170 control chromosomes (gnomAD). c.440delC has been reported in the literature in at least one individual affected with Propionic Acidemia (e.g. Campeau_2001). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 11592820). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Both submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.