ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.5255A>G (p.Lys1752Arg)

gnomAD frequency: 0.00004  dbSNP: rs864622373
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000206031 SCV000260335 uncertain significance Neurofibromatosis, type 1 2023-12-13 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 1731 of the NF1 protein (p.Lys1731Arg). This variant is present in population databases (no rsID available, gnomAD 0.02%). 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: 220078). 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 RCV002317736 SCV000670384 likely benign Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-01-16 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000761161 SCV000891077 uncertain significance Retinoblastoma 2017-04-04 criteria provided, single submitter clinical testing
GeneDx RCV001753612 SCV002005368 uncertain significance not provided 2024-10-24 criteria provided, single submitter clinical testing Observed in a patient with retinoblastoma (PMID: 34301788); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34301788)
Genome-Nilou Lab RCV000206031 SCV002560526 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing

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