ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1004A>G (p.Asn335Ser)

gnomAD frequency: 0.00001  dbSNP: rs758212945
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000558546 SCV000628340 uncertain significance Neurofibromatosis, type 1 2023-10-26 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 335 of the NF1 protein (p.Asn335Ser). This variant is present in population databases (rs758212945, gnomAD 0.007%). 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: 457510). 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.
Ambry Genetics RCV002316482 SCV000666807 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.
Genome-Nilou Lab RCV000558546 SCV002561856 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Medical Genetics, University of Parma RCV000558546 SCV002567763 uncertain significance Neurofibromatosis, type 1 2022-08-17 criteria provided, single submitter clinical testing

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