ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3811A>G (p.Met1271Val)

gnomAD frequency: 0.00001  dbSNP: rs746583007
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000529172 SCV000628547 uncertain significance Neurofibromatosis, type 1 2024-01-05 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 1271 of the NF1 protein (p.Met1271Val). This variant is present in population databases (rs746583007, gnomAD 0.003%). 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: 457669). 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.
Ambry Genetics RCV002316501 SCV000666786 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2023-01-23 criteria provided, single submitter clinical testing The p.M1271V variant (also known as c.3811A>G), located in coding exon 28 of the NF1 gene, results from an A to G substitution at nucleotide position 3811. The methionine at codon 1271 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.
Fulgent Genetics, Fulgent Genetics RCV000764109 SCV000895077 uncertain significance Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV001755805 SCV002007293 uncertain significance not provided 2021-08-18 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25486365, 22807134)
Genome-Nilou Lab RCV000529172 SCV002560333 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing

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