ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.2054C>A (p.Thr685Asn)

dbSNP: rs876658190
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001944474 SCV002131734 uncertain significance Neurofibromatosis, type 1 2023-07-16 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 685 of the NF1 protein (p.Thr685Asn). 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: 1366001). This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (gnomAD no frequency).
Ambry Genetics RCV002422922 SCV002727567 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2020-06-26 criteria provided, single submitter clinical testing The p.T685N variant (also known as c.2054C>A), located in coding exon 18 of the NF1 gene, results from a C to A substitution at nucleotide position 2054. The threonine at codon 685 is replaced by asparagine, an amino acid with 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.
PreventionGenetics, part of Exact Sciences RCV004552065 SCV004800397 uncertain significance NF1-related disorder 2024-02-23 no assertion criteria provided clinical testing The NF1 c.2054C>A variant is predicted to result in the amino acid substitution p.Thr685Asn. This variant was reported in an individual with phaeochromocytoma (supplementary table 5 patient #117, Ben Aim et al 2019. PubMed ID: 30877234). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/1366001/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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