Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000020391 | SCV002290808 | likely pathogenic | Pyruvate carboxylase deficiency | 2023-12-10 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu1137Valfs*34) in the PC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the PC protein. This variant is present in population databases (rs113994148, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with pyruvate carboxylase deficiency (PMID: 18676167). This variant is also known as c.3499–3500delCT (p. L1137VfsX1170). ClinVar contains an entry for this variant (Variation ID: 21229). This variant disrupts the C-terminus of the PC protein. Other variant(s) that disrupt this region (p.Glu1146Glyfs*26) have been observed in individuals with PC-related conditions (PMID: 23430542). This suggests that this may be a clinically significant region of the protein. 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. |
Baylor Genetics | RCV000020391 | SCV004202810 | pathogenic | Pyruvate carboxylase deficiency | 2023-06-12 | criteria provided, single submitter | clinical testing |