ClinVar Miner

Submissions for variant NM_000455.5(STK11):c.374+1A>G

dbSNP: rs1131690951
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492655 SCV000580944 pathogenic Hereditary cancer-predisposing syndrome 2015-02-10 criteria provided, single submitter clinical testing The c.374+1A>G intronic pathogenic mutation results from an A to G substitution one nucleotide after coding exon 2 of the STK11 gene. This mutation has been identified in multiple individuals with Peutz-Jeghers syndrome to date (Resta N, Hum. Mutat. 2002 Jul; 20(1):78-9. Aretz S, Hum. Mutat. 2005 Dec; 26(6):513-9. Mehenni H, Dig. Dis. Sci. 2007 Aug; 52(8):1924-33.). Additionally, RNA analysis has demonstrated that this alteration leads to the use of multiple downstream aberrant 3' splice sites, causing various frameshift transcripts that translationally result in alternate stop codons (Hastings ML, Nat. Struct. Mol. Biol. 2005 Jan; 12(1):54-9.). Based on the available evidence, c.374+1A>G is classified as a pathogenic mutation.
Invitae RCV001214909 SCV001386617 pathogenic Peutz-Jeghers syndrome 2022-01-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 15608654). ClinVar contains an entry for this variant (Variation ID: 428788). This variant has been observed in individuals with clinical features of Peutz-Jeghers syndrome (PMID: 12112668, 16287113; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 2 of the STK11 gene. It does not directly change the encoded amino acid sequence of the STK11 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product.
Genome-Nilou Lab RCV001214909 SCV002057361 pathogenic Peutz-Jeghers syndrome 2021-07-15 criteria provided, single submitter clinical testing

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