ClinVar Miner

Submissions for variant NM_030962.3(SBF2):c.1424A>G (p.Gln475Arg) (rs199894823)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000206478 SCV000260833 uncertain significance Charcot-Marie-Tooth disease type 4 2019-12-09 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 475 of the SBF2 protein (p.Gln475Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs199894823, ExAC 0.04%). This variant has not been reported in the literature in individuals with an SBF2-related disease. ClinVar contains an entry for this variant (Variation ID: 220352). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on SBF2 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Clinical Services Laboratory,Illumina RCV001094223 SCV000375075 uncertain significance Charcot-Marie-Tooth disease, type 4B2 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000413369 SCV000492176 uncertain significance not provided 2016-11-30 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SBF2 gene. The Q475R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The Q475R variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Athena Diagnostics Inc RCV000413369 SCV001145361 uncertain significance not provided 2019-05-10 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory,London Health Sciences Centre RCV001172793 SCV001335862 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing

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