ClinVar Miner

Submissions for variant NM_000532.5(PCCB):c.1514T>C (p.Ile505Thr)

gnomAD frequency: 0.00004  dbSNP: rs1353542774
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001247013 SCV001420410 likely pathogenic Propionic acidemia 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 505 of the PCCB protein (p.Ile505Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of propionic acidemia (Invitae). ClinVar contains an entry for this variant (Variation ID: 971266). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PCCB protein function with a positive predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV002568671 SCV003575593 uncertain significance Inborn genetic diseases 2021-10-12 criteria provided, single submitter clinical testing The c.1514T>C (p.I505T) alteration is located in exon 15 (coding exon 15) of the PCCB gene. This alteration results from a T to C substitution at nucleotide position 1514, causing the isoleucine (I) at amino acid position 505 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV001247013 SCV004205181 likely pathogenic Propionic acidemia 2023-10-18 criteria provided, single submitter clinical testing
Natera, Inc. RCV001247013 SCV002081499 uncertain significance Propionic acidemia 2021-05-03 no assertion criteria provided clinical testing

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