ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.6424A>C (p.Ser2142Arg)

dbSNP: rs1135402886
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002314852 SCV000663158 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2019-03-14 criteria provided, single submitter clinical testing The p.S2121R variant (also known as c.6361A>C), located in coding exon 41 of the NF1 gene, results from an A to C substitution at nucleotide position 6361. The serine at codon 2121 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000497060 SCV000753565 uncertain significance Neurofibromatosis, type 1 2023-10-29 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 2121 of the NF1 protein (p.Ser2121Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurofibromatosis, type 1 (PMID: 28961165). ClinVar contains an entry for this variant (Variation ID: 431670). 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 expected to disrupt NF1 protein function with a positive 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.
Genome-Nilou Lab RCV000497060 SCV002560962 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Medical Genetics, University of Parma RCV000497060 SCV000588815 uncertain significance Neurofibromatosis, type 1 2017-02-02 no assertion criteria provided clinical testing

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