ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.1108C>T (p.Pro370Ser) (rs878853862)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000233817 SCV000284371 uncertain significance Neurofibromatosis, type 1 2016-01-12 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 370 of the NF1 protein (p.Pro370Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a NF1-related disease. 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. In summary, this is a novel missense change that is not predicted to affect protein function or cause disease. However, the evidence is insufficient at this time to prove that conclusively. It has been classified as a Variant of Uncertain Significance.
GeneDx RCV000681022 SCV000808472 uncertain significance not provided 2017-03-15 criteria provided, single submitter clinical testing This variant is denoted NF1 c.1108C>T at the cDNA level, p.Pro370Ser (P370S) at the protein level, and results in the change of a Proline to a Serine (CCT>TCT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NF1 Pro370Ser was not observed in large population cohorts (NHLBI Exome Sequencing Project, The 1000 Genomes Consortium 2015, Lek 2016). Since Proline and Serine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. NF1 Pro370Ser occurs at a position that is not conserved and is not located in a known functional domain. In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether NF1 Pro370Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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