Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000414365 | SCV000492080 | uncertain significance | not specified | 2016-12-02 | criteria provided, single submitter | clinical testing | The T152A variant in the SSR4 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The T152A variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The T152A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However this substitution occurs at a position that is not conserved, and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, we interpret T152A as a variant of uncertain significance |
Institute for Clinical Genetics, |
RCV002521420 | SCV002010635 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002521420 | SCV003465792 | uncertain significance | not provided | 2024-08-04 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 152 of the SSR4 protein (p.Thr152Ala). This variant is present in population databases (rs782385685, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with SSR4-related conditions. ClinVar contains an entry for this variant (Variation ID: 373487). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Not Available". 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. |