ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.469A>G (p.Ile157Val)

dbSNP: rs1555606118
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002316649 SCV000666787 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2019-05-14 criteria provided, single submitter clinical testing The p.I157V variant (also known as c.469A>G), located in coding exon 4 of the NF1 gene, results from an A to G substitution at nucleotide position 469. The isoleucine at codon 157 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001066379 SCV001231386 uncertain significance Neurofibromatosis, type 1 2024-11-22 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 157 of the NF1 protein (p.Ile157Val). 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: 481959). 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 80%. 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.
Genome-Nilou Lab RCV001066379 SCV002561466 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004553271 SCV004106900 uncertain significance NF1-related disorder 2023-08-01 criteria provided, single submitter clinical testing The NF1 c.469A>G variant is predicted to result in the amino acid substitution p.Ile157Val. This variant has been reported in an individual with breast cancer (Jarhelle et al. 2019. PubMed ID: 31882575). An alternate substitution of this amino acid (p.Ile157Asn) has been reported in an individual with neurofibromatosis (De Luca et al. 2004. PubMed ID: 15146469). This c.469A>G (p.Ile157Val) variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating it is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV003465206 SCV004190722 uncertain significance Juvenile myelomonocytic leukemia 2023-05-19 criteria provided, single submitter clinical testing

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