ClinVar Miner

Submissions for variant NM_001330588.2(TPP2):c.2237T>A (p.Ile746Asn)

gnomAD frequency: 0.00004  dbSNP: rs148250766
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000794004 SCV000933386 uncertain significance Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency 2023-07-07 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 640880). This variant has not been reported in the literature in individuals affected with TPP2-related conditions. This variant is present in population databases (rs148250766, gnomAD 0.005%). This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 746 of the TPP2 protein (p.Ile746Asn).
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224471 SCV003920588 uncertain significance Immunodeficiency 78 with autoimmunity and developmental delay 2022-10-28 criteria provided, single submitter clinical testing This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.007% (3/41478) (https://gnomad.broadinstitute.org/variant/13-102644618-T-A?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:640880). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Ambry Genetics RCV004965738 SCV005527031 uncertain significance Inborn genetic diseases 2024-09-11 criteria provided, single submitter clinical testing The c.2237T>A (p.I746N) alteration is located in exon 18 (coding exon 18) of the TPP2 gene. This alteration results from a T to A substitution at nucleotide position 2237, causing the isoleucine (I) at amino acid position 746 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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