Submissions for variant NM_003977.4(AIP):c.919dup (p.Arg307fs)

dbSNP: rs267606589

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV003343605	SCV004051445	likely pathogenic	Hereditary cancer-predisposing syndrome	2023-08-09	criteria provided, single submitter	clinical testing	The c.919dupC variant, located in coding exon 6 of the AIP gene, results from a duplication of C at nucleotide position 919, causing a translational frameshift with a predicted alternate stop codon (p.Q307Pfs*70). This alteration occurs at the 3' terminus of theAIP gene, is not expected to trigger nonsense-mediated mRNAdecay and results in the elongation of the protein by 45 amino acids. This frameshift impacts the last 24amino acids of the native protein. However, frameshifts are typically deleterious in nature and a significant portion of the protein is affected (Ambry internal data). This alteration has been identified in pediatric patients with pituitary macroadenomas (Stratakis CA et al. Clin Genet, 2010 Nov;78:457-63; Beckers A et al. Endocr Rev, 2013 Apr;34:239-77). Of note, this variant is designated as c.919insC, p.Gln307ProfsX104, and Q307fsX104 in published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Invitae	RCV003764656	SCV004642556	uncertain significance	not provided	2024-01-15	criteria provided, single submitter	clinical testing	This sequence change results in a frameshift in the AIP gene (p.Arg307Profs*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 24 amino acid(s) of the AIP protein and extend the protein by an uncertain number of additional amino acid residue(s). This variant is not present in population databases (gnomAD no frequency). 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: 41215). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
GeneReviews	RCV000034114	SCV000058044	probable-pathogenic	Somatotroph adenoma	2012-06-21	no assertion criteria provided	curation	Converted during submission to Likely pathogenic.