Submissions for variant NM_003620.4(PPM1D):c.1349T>G (p.Leu450Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
DASA	RCV002308503	SCV002600254	likely pathogenic	Intellectual developmental disorder with gastrointestinal difficulties and high pain threshold	2022-11-03	criteria provided, single submitter	clinical testing	The c.1349T>G;p.(Leu450*) variant creates a premature translational stop signal in the PPM1D gene. It is expected to result in an absent or disrupted protein product - PVS1. The variant is present at low allele frequencies population databases (rs1163049039 – gnomAD 0.00006570%; ABraOM no frequency - https://abraom.ib.usp.br/) - PM2_supporting. In summary, the currently available evidence indicates that the variant is likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003099105	SCV003278293	uncertain significance	not provided	2022-04-24	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with PPM1D-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu450*) in the PPM1D gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 156 amino acid(s) of the PPM1D protein.