ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.479G>C (p.Arg160Thr) (rs199474752)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000538243 SCV000628622 likely pathogenic Neurofibromatosis, type 1 2017-12-08 criteria provided, single submitter clinical testing This sequence change replaces arginine with threonine at codon 160 of the NF1 protein (p.Arg160Thr). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and threonine. This variant also falls at the last nucleotide of exon 4 of the NF1 coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency). This variant has been reported in 2 individuals affected with neurofibromatosis type 1 (PMID: 21838856, 17311297). ClinVar contains an entry for this variant (Variation ID: 68353). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this missense change disrupts normal splicing of exon 4 (PMID: 17311297). 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.
UniProtKB/Swiss-Prot RCV000059206 SCV000090735 not provided not provided no assertion provided not provided

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