Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001852689 | SCV002245646 | pathogenic | not provided | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg81*) in the AIP gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AIP are known to be pathogenic (PMID: 23321498, 26186299). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with AIP-related conditions (PMID: 18381572). ClinVar contains an entry for this variant (Variation ID: 41167). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV004619192 | SCV005117416 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-03-22 | criteria provided, single submitter | clinical testing | The p.R81* variant (also known as c.241C>T), located in coding exon 2 of the AIP gene, results from a C to T substitution at nucleotide position 241. This changes the amino acid from an arginine to a stop codon within coding exon 2. This variant has been reported in multiple individuals diagnosed with pituitary adenomas (Leontiou CA et al. J Clin Endocrinol Metab, 2008 Jun;93:2390-401; Toledo RA et al. Clinics (Sao Paulo), 2010 Apr;65:407-15; Dutta P et al. J Clin Endocrinol Metab, 2019 Aug;104:3539-3544; Guaraldi F et al. Pituitary, 2012 Dec;15 Suppl 1:S61-7; Gaspar LM et al. J Endocrinol Invest, 2023 Nov;46:2299-2307; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (Leontiou CA et al. J Clin Endocrinol Metab, 2008 Jun;93:2390-401). (Toledo RA et al. Clinics (Sao Paulo), 2010 Apr;65:407-15). (Dutta P et al. J Clin Endocrinol Metab, 2019 Aug;104:3539-3544). (Guaraldi F et al. Pituitary, 2012 Dec;15 Suppl 1:S61-7). (Gaspar LM et al. J Endocrinol Invest, 2023 Nov;46:2299-2307). |
| Gene |
RCV000034066 | SCV000057996 | not provided | Somatotroph adenoma | no assertion provided | literature only |