ClinVar Miner

Submissions for variant NM_003978.5(PSTPIP1):c.764C>T (p.Thr255Met) (rs766895096)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489849 SCV000577488 uncertain significance not provided 2018-02-15 criteria provided, single submitter clinical testing The T255M variant in the PSTPIP1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The T255M variant is observed in 1/63804 (0.002%) alleles from individuals of European Non-Finnish background in the ExAC dataset (Lek et al., 2016). The T255M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position in the F-BAR domain that is not conserved across species. However, in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret T255M as a variant of uncertain significance.
Invitae RCV001036647 SCV001200022 uncertain significance Pyogenic arthritis-pyoderma gangrenosum-acne syndrome 2020-09-08 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 255 of the PSTPIP1 protein (p.Thr255Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs766895096, ExAC 0.002%). This variant has not been reported in the literature in individuals with PSTPIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 426913). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.