ClinVar Miner

Submissions for variant NM_000532.5(PCCB):c.1301C>T (p.Ala434Val) (rs751538672)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670133 SCV000794950 likely pathogenic Propionyl-CoA carboxylase deficiency 2017-10-26 criteria provided, single submitter clinical testing
Invitae RCV000670133 SCV000931377 pathogenic Propionyl-CoA carboxylase deficiency 2018-10-21 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 434 of the PCCB protein (p.Ala434Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs751538672, ExAC 0.03%). This variant has been observed as homozygous, or on the opposite chromosome (in trans) from other pathogenic variants in individuals affected with propionic acidemia  (PMID: 24863100). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 554490). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic.

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