ClinVar Miner

Submissions for variant NM_000282.4(PCCA):c.722del (p.Gly241fs) (rs745571507)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666232 SCV000790490 likely pathogenic Propionic acidemia 2017-04-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000666232 SCV000917968 pathogenic Propionic acidemia 2018-01-05 criteria provided, single submitter clinical testing Variant summary: The PCCA c.722delG (p.Gly241ValfsX19) variant results in a premature termination codon, predicted to cause a truncated or absent PCCA protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 8/245002 control chromosomes in gnomAD at a frequency of 0.0000327, which does not exceed the estimated maximal expected allele frequency of a pathogenic PCCA variant (0.003446). This variant has been identified in at least 2 patients with Propionic Acidemia, both of whom were homozygous and had early onset of symptoms (Perez_2003, Tuchman_2008). Taken together, this variant is classified as pathogenic.
Invitae RCV000666232 SCV001421893 pathogenic Propionic acidemia 2020-10-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly241Valfs*19) in the PCCA gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs745571507, ExAC 0.006%). This variant has been observed in an individual affected with propionic acidemia (PMID: 12559849). ClinVar contains an entry for this variant (Variation ID: 551231). Loss-of-function variants in PCCA are known to be pathogenic (PMID: 15464417). For these reasons, this variant has been classified as Pathogenic.
Natera, Inc. RCV000666232 SCV001455846 pathogenic Propionic acidemia 2020-09-16 no assertion criteria provided clinical testing

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