ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4444A>G (p.Ile1482Val)

dbSNP: rs1060500362
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000459730 SCV000542185 uncertain significance Neurofibromatosis, type 1 2024-06-21 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 1461 of the NF1 protein (p.Ile1461Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurofibromatosis type 1 (PMID: 26740943). ClinVar contains an entry for this variant (Variation ID: 404580). 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.
Ambry Genetics RCV002318996 SCV001184120 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-05-30 criteria provided, single submitter clinical testing The c.4381A>G (p.I1461V) alteration is located in exon 33 (coding exon 33) of the NF1 gene. This alteration results from a A to G substitution at nucleotide position 4381, causing the isoleucine (I) at amino acid position 1461 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV000459730 SCV002560425 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004551514 SCV004115725 uncertain significance NF1-related disorder 2022-11-17 criteria provided, single submitter clinical testing The NF1 c.4444A>G variant is predicted to result in the amino acid substitution p.Ile1482Val. This variant has been reported in an individual with neurofibromatosis type 1 (Table S1, reported as NM_000267:c.4381A>G (p.Ile1461Val), Bianchessi et al. 2015. PubMed ID: 26740943). To our knowledge, this variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. it is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/404580/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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