ClinVar Miner

Submissions for variant NM_003977.4(AIP):c.807C>T (p.Phe269=) (rs139407567)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000034108 SCV000373583 likely benign Somatotroph adenoma 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Ambry Genetics RCV000571925 SCV000672424 likely benign Hereditary cancer-predisposing syndrome 2020-03-20 criteria provided, single submitter clinical testing RNA Studies;Subpopulation frequency in support of benign classification
Invitae RCV000951118 SCV001097483 likely benign not provided 2020-12-04 criteria provided, single submitter clinical testing
Baylor Genetics RCV000034108 SCV001483039 uncertain significance Somatotroph adenoma 2018-12-21 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing [PMID 18381572, 25184284]
GeneDx RCV000951118 SCV001772730 likely benign not provided 2019-07-17 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 2200621, 26186299, 21753072, 17609395, 28220018, 23038625, 18381572, 25184284, 20506337, 18410548)
GeneReviews RCV000034108 SCV000058038 pathologic Somatotroph adenoma 2012-06-21 no assertion criteria provided curation Converted during submission to Pathogenic.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000951118 SCV001548583 likely benign not provided no assertion criteria provided clinical testing The AIP p.F269F variant was identified in 5 individuals with pituitary adenoma, acromegaly, gigantism, or macroadenoma, however the variant was also identified in unaffected family members (DeSousa_2017_PMID:28220018; Preda_2014_PMID:25184284; Oriola_2012_PMID:23038625; Igreja_2010_PMID:20506337). Functional studies reveal that individuals and in vitro models with this variant have decreased AIP mRNA expression compared to control (Igreja_2010_PMID:20506337). The variant was identified in dbSNP (ID: rs139407567), LOVD 3.0 and ClinVar (classified as uncertain significance by Ambry Genetics and as likely benign by Illumina and Invitae). The variant was identified in control databases in 154 of 280240 chromosomes at a frequency of 0.0005495 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 112 of 127076 chromosomes (freq: 0.000881), South Asian in 21 of 30602 chromosomes (freq: 0.000686), Other in 4 of 7176 chromosomes (freq: 0.000557), Latino in 10 of 35398 chromosomes (freq: 0.000283), African in 6 of 24736 chromosomes (freq: 0.000243) and European (Finnish) in 1 of 25074 chromosomes (freq: 0.00004), but was not observed in the Ashkenazi Jewish, or East Asian populations. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000951118 SCV001741536 uncertain significance not provided no assertion criteria provided clinical testing

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