ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1260+1G>T

dbSNP: rs267606603
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000691582 SCV000819368 pathogenic Neurofibromatosis, type 1 2020-08-09 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 11 of the NF1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individual(s) with neurofibromatosis type 1 (PMID: 10677298, Invitae). ClinVar contains an entry for this variant (Variation ID: 570670). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002424625 SCV002679238 likely pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2018-08-10 criteria provided, single submitter clinical testing The c.1260+1G>T intronic variant results from a G to T substitution one nucleotide after coding exon 11 of the NF1 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.

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