ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.7199A>G (p.His2400Arg)

dbSNP: rs1597858362
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000821308 SCV000962062 uncertain significance Neurofibromatosis, type 1 2018-10-20 criteria provided, single submitter clinical testing 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NF1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with arginine at codon 2379 of the NF1 protein (p.His2379Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine.
Ambry Genetics RCV002363160 SCV002662717 likely pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2022-02-23 criteria provided, single submitter clinical testing The p.H2379R variant (also known as c.7136A>G), located in coding exon 48 of the NF1 gene, results from an A to G substitution at nucleotide position 7136. The histidine at codon 2379 is replaced by arginine, an amino acid with highly similar properties. The variant was detected in siblings with a clinical diagnosis of neurofibromatosis type 1 (NF1) (Ambry internal data). This variant is assumed to be the result of a de novo mutation or germline mosaicism in one individual with NF1 features at another laboratory (personal communication). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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