Submissions for variant NM_001122764.3(PPOX):c.1330_1331del (p.Leu444fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003562301	SCV004292947	likely pathogenic	not provided	2023-12-28	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu444Aspfs*8) in the PPOX gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 34 amino acid(s) of the PPOX protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with variegate porphyria (PMID: 12859407). It has also been observed to segregate with disease in related individuals. This variant disrupts the C-terminus of the PPOX protein. Other variant(s) that disrupt this region (p.Tyr451*) have been observed in individuals with PPOX-related conditions (PMID: 19656455). 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.
GeneDx	RCV003562301	SCV005325162	likely pathogenic	not provided	2023-08-28	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation, as the last 34 amino acids are replaced with 7 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 12859407)