Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001214534 | SCV001386218 | uncertain significance | Alstrom syndrome | 2019-06-28 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with asparagine at codon 488 of the ALMS1 protein (p.Lys488Asn). The lysine residue is weakly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ALMS1-related disease. 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, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002393495 | SCV002698785 | uncertain significance | Cardiovascular phenotype | 2022-05-10 | criteria provided, single submitter | clinical testing | The p.K488N variant (also known as c.1464A>C), located in coding exon 8 of the ALMS1 gene, results from an A to C substitution at nucleotide position 1464. The lysine at codon 488 is replaced by asparagine, an amino acid with similar properties. This amino acid position is poorly conserved in available 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. |