ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3365A>G (p.Asp1122Gly)

dbSNP: rs1597719461
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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 RCV002445167 SCV001181534 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2019-06-11 criteria provided, single submitter clinical testing The p.D1122G variant (also known as c.3365A>G), located in coding exon 26 of the NF1 gene, results from an A to G substitution at nucleotide position 3365. The aspartic acid at codon 1122 is replaced by glycine, an amino acid with similar properties. This amino acid position is 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 RCV003495227 SCV004364058 uncertain significance Neurofibromatosis, type 1 2023-12-19 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1122 of the NF1 protein (p.Asp1122Gly). This variant is not present in population databases (gnomAD no frequency). 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: 823670). 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%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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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