ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.245C>T (p.Ser82Phe)

dbSNP: rs199474729
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000659959 SCV000781866 pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
GeneDx RCV000059172 SCV000808256 uncertain significance not provided 2018-07-11 criteria provided, single submitter clinical testing The S82F variant has been published in association with neurofibromatosis type 1; however, no segregation information is available (Kluwe et al., 2002; Griffiths et al., 2007). Additionally, the variant is observed in 2/246798 (0.0008%) alleles in large population cohorts (Lek et al., 2016). S82F is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV000659959 SCV001479000 likely pathogenic Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
Invitae RCV000659959 SCV001590554 pathogenic Neurofibromatosis, type 1 2023-02-03 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 82 of the NF1 protein (p.Ser82Phe). This variant is present in population databases (rs199474729, gnomAD 0.003%). This missense change has been observed in individual(s) with neurofibromatosis, type 1 (PMID: 11857752; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 68320). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
UniProtKB/Swiss-Prot RCV000059172 SCV000090701 not provided not provided no assertion provided not provided

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