ClinVar Miner

Submissions for variant NM_002972.4(SBF1):c.4639C>T (p.Arg1547Trp)

gnomAD frequency: 0.00027  dbSNP: rs370182117
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001002004 SCV001159820 uncertain significance Charcot-Marie-Tooth disease type 4B3 2018-08-05 criteria provided, single submitter clinical testing The SBF1 c.4639C>T; p.Arg1547Trp variant (rs370182117), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found in the general population with an overall allele frequency of 0.03% (75/276800 alleles) in the Genome Aggregation Database. The arginine at codon 1547 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Due to limited information, the clinical significance of the p.Arg1547Trp variant is uncertain at this time.
GeneDx RCV001766820 SCV001991649 uncertain significance not provided 2019-08-01 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001766820 SCV002178758 uncertain significance not provided 2023-12-21 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1547 of the SBF1 protein (p.Arg1547Trp). This variant is present in population databases (rs370182117, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with SBF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 811714). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SBF1 protein function with a positive predictive value of 80%. 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.

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