ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4333A>G (p.Ile1445Val)

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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 RCV003072868 SCV003472691 uncertain significance Neurofibromatosis, type 1 2022-06-09 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1424 of the NF1 protein (p.Ile1424Val). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function.
Ambry Genetics RCV004560035 SCV005048164 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2023-07-06 criteria provided, single submitter clinical testing The p.I1424V variant (also known as c.4270A>G) is located in coding exon 32 of the NF1 gene. The isoleucine at codon 1424 is replaced by valine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 32. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV004593152 SCV005081231 uncertain significance not provided 2023-09-06 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Identified among unaffected controls only in breast and biliary tract cancer case-control studies (Momozawa et al., 2018; Okawa et al., 2023); This variant is associated with the following publications: (PMID: 36243179, 25486365, 22807134, 30287823)

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