ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3371G>A (p.Ser1124Asn)

gnomAD frequency: 0.00004  dbSNP: rs374472758
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000527707 SCV000628512 uncertain significance Neurofibromatosis, type 1 2023-11-28 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1124 of the NF1 protein (p.Ser1124Asn). This variant is present in population databases (rs374472758, gnomAD 0.03%). 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: 457643). 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.
Fulgent Genetics, Fulgent Genetics RCV000764107 SCV000895075 uncertain significance Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV002448634 SCV001181553 likely benign Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2017-12-06 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.
GeneDx RCV001574886 SCV001801773 uncertain significance not provided 2022-09-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 28977029, 25486365, 2121369)
Sema4, Sema4 RCV001020116 SCV002527503 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-30 criteria provided, single submitter curation

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