ClinVar Miner

Submissions for variant NM_030962.4(SBF2):c.4733A>G (p.Lys1578Arg)

gnomAD frequency: 0.00001  dbSNP: rs775360425
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000389514 SCV000375038 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.
Genetic Services Laboratory, University of Chicago RCV000504119 SCV000596931 uncertain significance not specified 2016-04-21 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001222975 SCV001395101 uncertain significance Charcot-Marie-Tooth disease type 4 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 1578 of the SBF2 protein (p.Lys1578Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is present in population databases (rs775360425, ExAC 0.004%). This variant has not been reported in the literature in individuals affected with SBF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 306580). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Ambry Genetics RCV002338883 SCV002639115 uncertain significance Inborn genetic diseases 2021-08-02 criteria provided, single submitter clinical testing The p.K1578R variant (also known as c.4733A>G), located in coding exon 35 of the SBF2 gene, results from an A to G substitution at nucleotide position 4733. The lysine at codon 1578 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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