ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.2135A>G (p.His712Arg)

dbSNP: rs199474727
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002318948 SCV001175179 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2018-12-27 criteria provided, single submitter clinical testing The p.H712R variant (also known as c.2135A>G), located in coding exon 18 of the NF1 gene, results from an A to G substitution at nucleotide position 2135. The histidine at codon 712 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001854233 SCV002262054 uncertain significance Neurofibromatosis, type 1 2024-06-03 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 712 of the NF1 protein (p.His712Arg). This variant is present in population databases (rs199474727, gnomAD 0.0009%). 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: 68310). 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) performed at Invitae indicates that this missense variant is not expected to disrupt NF1 protein function with a negative predictive value of 95%. 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.
Genome-Nilou Lab RCV001854233 SCV002562001 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000059162 SCV000090691 not provided not provided no assertion provided not provided

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