Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001001087 | SCV001158222 | uncertain significance | Charcot-Marie-Tooth disease type 4B3 | 2019-03-04 | criteria provided, single submitter | clinical testing | The SBF1 c.1069A>G; p.Thr357Ala variant (rs746439204), to our knowledge, is not described in the medical literature or in gene-specific databases, and is observed on only 3 alleles in the Genome Aggregation Database. The threonine at codon 357 is weakly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is tolerated. However, due to the lack of clinical and functional data regarding this variant, its clinical significance cannot be determined with certainty. |
| Invitae | RCV001860502 | SCV002301960 | uncertain significance | not provided | 2021-09-17 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with alanine at codon 357 of the SBF1 protein (p.Thr357Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs746439204, ExAC 0.007%). 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: 811309). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |