Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001019700 | SCV001181091 | likely benign | Hereditary cancer-predisposing syndrome | 2022-02-20 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Invitae | RCV001203294 | SCV001374451 | uncertain significance | not provided | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 325 of the AIP protein (p.Arg325Gln). This variant is present in population databases (rs754619109, gnomAD 0.03%). This missense change has been observed in individual(s) with AIP-related conditions (PMID: 22319033, 24078436). ClinVar contains an entry for this variant (Variation ID: 823449). 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 not expected to disrupt AIP protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect AIP function (PMID: 27253664, 29632148, 34588620). 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. |
St. |
RCV003153889 | SCV003843051 | uncertain significance | Somatotroph adenoma | 2023-02-22 | criteria provided, single submitter | clinical testing | The AIP c.974G>A (p.Arg325Gln) missense change has a maximum subpopulation frequency of 0.031% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). This variant has been observed in individuals with pituitary adenomas (PMID: 22319033, 23371967, 24078436, 29455389). One individual also harbored a nonsense variant in AIP (PMID: 29455389). The variant segregated with disease in a parent and child with AIP-related conditions and the tumor of one individual showed loss of heterozygosity (PMID: 24078436). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and functional studies suggest that this variant is benign (PMID: 29632148, 34588620). In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
Baylor Genetics | RCV003153889 | SCV004193539 | uncertain significance | Somatotroph adenoma | 2023-09-24 | criteria provided, single submitter | clinical testing |