ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.5941A>G (p.Met1981Val)

gnomAD frequency: 0.00001  dbSNP: rs762935987
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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 RCV002316607 SCV000666720 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2017-11-03 criteria provided, single submitter clinical testing The p.M1960V variant (also known as c.5878A>G), located in coding exon 39 of the NF1 gene, results from an A to G substitution at nucleotide position 5878. The methionine at codon 1960 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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 RCV002526832 SCV003519800 uncertain significance Neurofibromatosis, type 1 2023-10-24 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1960 of the NF1 protein (p.Met1960Val). This variant is present in population databases (rs762935987, gnomAD 0.002%). 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: 481916). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NF1 protein function. 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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