Submissions for variant NM_001042492.3(NF1):c.3463G>A (p.Ala1155Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV002509948	SCV002818628	uncertain significance	not provided	2022-07-02	criteria provided, single submitter	clinical testing	Reported as a germline variant of uncertain significance in a healthy control individual in a case-control study of Japanese patients with breast cancer (Momozawa et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30287823, 25486365, 2121369, 22807134)
Labcorp Genetics (formerly Invitae), Labcorp	RCV003598144	SCV004551750	uncertain significance	Neurofibromatosis, type 1	2023-12-30	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1155 of the NF1 protein (p.Ala1155Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 30287823). ClinVar contains an entry for this variant (Variation ID: 1810461). 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.