ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.3572C>T (p.Thr1191Ile)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002904440 SCV003256197 likely pathogenic Neurofibromatosis, type 1 2023-10-04 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1191 of the NF1 protein (p.Thr1191Ile). This variant is not present in population databases (gnomAD no frequency). 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: 2047617). 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. This variant disrupts the p.Thr1191 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23047742, 25541118). 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.
Ambry Genetics RCV004990913 SCV005452010 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2024-08-16 criteria provided, single submitter clinical testing The p.T1191I variant (also known as c.3572C>T), located in coding exon 27 of the NF1 gene, results from a C to T substitution at nucleotide position 3572. The threonine at codon 1191 is replaced by isoleucine, an amino acid with similar 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. Based on the available evidence, the clinical significance of this variant remains unclear.

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