Submissions for variant NM_003978.5(PSTPIP1):c.1115C>T (p.Ala372Val)

gnomAD frequency: 0.00014  dbSNP: rs200188483

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000508173	SCV000604951	uncertain significance	not specified	2017-01-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000766644	SCV000616835	uncertain significance	not provided	2019-06-25	criteria provided, single submitter	clinical testing	Identified in a patient with primary immunodeficiency disease who was also hemizygous for a variant in the CD40LG gene, and identified in a patient with fever and lymphadenopathy who was also heterozygous for a variant in the FCN3 gene (Stray-Pedersen et al., 2016; Chi et al., 2018); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27577878, 30290665)
Invitae	RCV001212728	SCV001384322	uncertain significance	Pyogenic arthritis-pyoderma gangrenosum-acne syndrome	2023-08-08	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. 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. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 372 of the PSTPIP1 protein (p.Ala372Val). This variant is present in population databases (rs200188483, gnomAD 0.03%). This missense change has been observed in individual(s) with primary immunodeficiency and fevers with lymphadenopathy (PMID: 27577878, 30290665). ClinVar contains an entry for this variant (Variation ID: 440209).
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000766644	SCV002009984	likely benign	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002263717	SCV002542844	uncertain significance	Autoinflammatory syndrome	2019-09-01	criteria provided, single submitter	clinical testing