ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.5944-5A>G (rs267606604)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000000387 SCV000259361 pathogenic Neurofibromatosis, type 1 2016-05-12 criteria provided, single submitter clinical testing This sequence change falls in intron 39 of the NF1 mRNA. It does not directly change the encoded amino acid sequence of the NF1 protein. This variant is not present in population databases (rs267606604, ExAC no frequency). This variant has been reported to segregate with neurofibromatosis in 2 families (PMID: 7981692, 11704931). In both of these families, the affected parents and offspring carried this c.5944-5A>G variant, while the unaffected offspring did not. It has also been reported in 3 additional unrelated individuals with neurofibromatosis (PMID: 10712197, 18546366, 24789688). This variant is also known as A47768>G and IVS31-5A>G in the literature. ClinVar contains an entry for this variant (Variation ID: 359). Experimental studies have shown that this intronic change creates a cryptic splice acceptor site upstream of the canonical site, resulting in an insertion of 4 nucleotides (PMID: 7981692, 11704931). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000572936 SCV000670372 pathogenic Hereditary cancer-predisposing syndrome 2017-06-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Functionally-validated splicing mutation,Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Center for Human Genetics, Inc RCV000000387 SCV000782069 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
OMIM RCV000000387 SCV000020531 pathogenic Neurofibromatosis, type 1 2001-12-01 no assertion criteria provided literature only
OMIM RCV000000388 SCV000020532 pathogenic Neurofibromatosis, familial spinal 2001-12-01 no assertion criteria provided literature only

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