ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1373C>A (p.Pro458Gln)

dbSNP: rs781555047
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002319142 SCV001171543 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2019-01-30 criteria provided, single submitter clinical testing The p.P458Q variant (also known as c.1373C>A), located in coding exon 12 of the NF1 gene, results from a C to A substitution at nucleotide position 1373. The proline at codon 458 is replaced by glutamine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV002550763 SCV002979456 uncertain significance Neurofibromatosis, type 1 2022-09-14 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 458 of the NF1 protein (p.Pro458Gln). This variant is present in population databases (rs781555047, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 819038). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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