ClinVar Miner

Submissions for variant NM_000267.3(NF1):c.2495A>G (p.Asp832Gly) (rs1060500283)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000476226 SCV000542047 uncertain significance Neurofibromatosis, type 1 2020-05-21 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 832 of the NF1 protein (p.Asp832Gly). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a NF1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000569313 SCV000666782 uncertain significance Hereditary cancer-predisposing syndrome 2016-10-03 criteria provided, single submitter clinical testing The p.D832G variant (also known as c.2495A>G), located in coding exon 21 of the NF1 gene, results from an A to G substitution at nucleotide position 2495. The aspartic acid at codon 832 is replaced by glycine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 175000 alleles tested) in our clinical cohort. 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.
Baylor Genetics RCV001292906 SCV001481600 uncertain significance Juvenile myelomonocytic leukemia 2020-02-11 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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