Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000563836 | SCV000672440 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-04-27 | criteria provided, single submitter | clinical testing | The p.T35M variant (also known as c.104C>T), located in coding exon 2 of the AIP gene, results from a C to T substitution at nucleotide position 104. The threonine at codon 35 is replaced by methionine, an amino acid with similar properties. This amino acid position is highly conserved through mammals, but not in all available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001068537 | SCV001233654 | uncertain significance | not provided | 2023-12-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 35 of the AIP protein (p.Thr35Met). This variant is present in population databases (rs376797001, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with AIP-related conditions. ClinVar contains an entry for this variant (Variation ID: 485058). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AIP protein function. 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. |
| Baylor Genetics | RCV004569246 | SCV005059397 | uncertain significance | Somatotroph adenoma | 2024-03-30 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001068537 | SCV005384121 | uncertain significance | not provided | 2023-12-28 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |