ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.4173A>T (p.Arg1391Ser) (rs137854554)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Clinical Molecular Genetics Laboratory,Johns Hopkins All Children's Hospital RCV000000376 SCV000692352 pathogenic Neurofibromatosis, type 1 2016-03-29 no assertion criteria provided clinical testing
Invitae RCV000000376 SCV000816067 likely pathogenic Neurofibromatosis, type 1 2018-06-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 1391 of the NF1 protein (p.Arg1391Ser). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with neurofibromatosis type 1 (PMID: 9003501, 27322474). ClinVar contains an entry for this variant (Variation ID: 348). Experimental studies have shown that this missense change reduces the GTPase-activating function of the NF1 protein, and reduces its affinity for Ras (PMID: 9003501, 22807134, 7581973, 16513807). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000000376 SCV000020520 pathogenic Neurofibromatosis, type 1 1997-01-01 no assertion criteria provided literature only

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