ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.2996G>A (p.Arg999His) (rs1342942240)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000622213 SCV000738949 uncertain significance Cardiovascular phenotype 2016-01-04 criteria provided, single submitter clinical testing The p.R999H variant (also known as c.2996G>A), located in coding exon 24 of the FBN2 gene, results from a G to A substitution at nucleotide position 2996. The arginine at codon 999 is replaced by histidine, an amino acid with highly 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. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Invitae RCV000792037 SCV000931309 uncertain significance Congenital contractural arachnodactyly 2019-07-15 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 999 of the FBN2 protein (p.Arg999His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FBN2-related disease. ClinVar contains an entry for this variant (Variation ID: 519806). 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: Probably Damaging; Align-GVGD: Class C0). 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.
Mayo Clinic Laboratories, Mayo Clinic RCV001509252 SCV001715864 uncertain significance not provided 2020-02-19 criteria provided, single submitter clinical testing

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