ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.6705-1G>C

dbSNP: rs1060500356
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000457846 SCV000542176 pathogenic Neurofibromatosis, type 1 2021-06-17 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. Disruption of this splice site has been observed in individuals with neurofibromatosis type 1 (PMID: 10712197, Invitae). ClinVar contains an entry for this variant (Variation ID: 404573). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 43 of the NF1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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).
Ambry Genetics RCV002365594 SCV002662203 likely pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2021-08-06 criteria provided, single submitter clinical testing The c.6642-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 44 of the NF1 gene. 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. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Baylor Genetics RCV003463850 SCV004190753 pathogenic Juvenile myelomonocytic leukemia 2023-03-30 criteria provided, single submitter clinical testing

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