ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.958G>C (p.Ala320Pro)

dbSNP: rs2066507272
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001061326 SCV001226064 likely pathogenic Neurofibromatosis, type 1 2025-01-23 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 320 of the NF1 protein (p.Ala320Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of NF1-related conditions (PMID: 31573083; internal data). ClinVar contains an entry for this variant (Variation ID: 855966). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt NF1 protein function with a positive predictive value of 95%. This variant disrupts the p.Ala320 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (internal data). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx RCV001760025 SCV002007869 uncertain significance not provided 2021-03-23 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with multiple cafe au lait macules (Castellanos et al., 2020); This variant is associated with the following publications: (PMID: 31573083)
Genome-Nilou Lab RCV001061326 SCV002561852 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing

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