Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001247192 | SCV001420600 | uncertain significance | Alstrom syndrome | 2019-10-02 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with proline at codon 2607 of the ALMS1 protein (p.Ser2607Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline. This variant is present in population databases (rs532551687, ExAC 0.03%). This variant has not been reported in the literature in individuals with ALMS1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 | RCV002411910 | SCV002669613 | uncertain significance | Cardiovascular phenotype | 2019-04-01 | criteria provided, single submitter | clinical testing | The p.S2607P variant (also known as c.7819T>C), located in coding exon 10 of the ALMS1 gene, results from a T to C substitution at nucleotide position 7819. The serine at codon 2607 is replaced by proline, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species; however, proline is the reference amino acid in other vertebrate species. 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. |
Natera, |
RCV001247192 | SCV002082885 | uncertain significance | Alstrom syndrome | 2021-09-30 | no assertion criteria provided | clinical testing |