ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.1465T>G (p.Tyr489Asp)

dbSNP: rs2066786672
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001044577 SCV001208382 uncertain significance Neurofibromatosis, type 1 2023-11-09 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 489 of the NF1 protein (p.Tyr489Asp). 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: 842198). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NF1 protein function. 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.
Sema4, Sema4 RCV002256653 SCV002527403 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-16 criteria provided, single submitter curation
Genome-Nilou Lab RCV001044577 SCV002561918 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002393219 SCV002701236 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-02-28 criteria provided, single submitter clinical testing The p.Y489D variant (also known as c.1465T>G), located in coding exon 13 of the NF1 gene, results from a T to G substitution at nucleotide position 1465. The tyrosine at codon 489 is replaced by aspartic acid, an amino acid with highly dissimilar properties. 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.

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