Submissions for variant NM_003978.5(PSTPIP1):c.821C>T (p.Thr274Met)

dbSNP: rs2076440871

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001316906	SCV001507546	uncertain significance	Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	2023-06-09	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 are conflicting or provide insufficient evidence to determine the effect of this variant on PSTPIP1 function (PMID: 29432774). 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 PSTPIP1 protein function. ClinVar contains an entry for this variant (Variation ID: 1017713). This missense change has been observed in individual(s) with common variable immunodeficiency (PMID: 29432774). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 274 of the PSTPIP1 protein (p.Thr274Met).
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001702892	SCV001927527	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001702892	SCV001970744	uncertain significance	not provided		no assertion criteria provided	clinical testing