ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.5244C>G (p.His1748Gln)

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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 RCV002338451 SCV002641463 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2020-05-07 criteria provided, single submitter clinical testing The p.H1727Q variant (also known as c.5181C>G), located in coding exon 36 of the NF1 gene, results from a C to G substitution at nucleotide position 5181. The histidine at codon 1727 is replaced by glutamine, 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 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 RCV003598087 SCV004548724 uncertain significance Neurofibromatosis, type 1 2023-04-11 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 1745859). This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is present in population databases (rs749010787, gnomAD 0.0009%). This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1727 of the NF1 protein (p.His1727Gln).

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