ClinVar Miner

Submissions for variant NM_003978.5(PSTPIP1):c.1115C>T (p.Ala372Val) (rs200188483)

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Total submissions: 3
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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 2017-09-28 criteria provided, single submitter clinical testing The A372V variant has been observed previously in a patient with primary immunodeficiency disease; however, the patient was also hemizygous for a variant in the CD40LG gene (Stray-Pedersen et al., 2016). The variant is observed in 5/17606 (0.028%) alleles from individuals of East Asian background in the ExAC dataset (Lek et al., 2016). A372V is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001212728 SCV001384322 uncertain significance Pyogenic arthritis-pyoderma gangrenosum-acne syndrome 2019-06-06 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 372 of the PSTPIP1 protein (p.Ala372Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs200188483, ExAC 0.03%). This variant has been observed in several individuals affected with primary immunodeficiency and fevers with lymphadenopathy (PMID: 27577878, 30290665). ClinVar contains an entry for this variant (Variation ID: 440209). 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: Probably Damaging; 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.

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