Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000697141 | SCV000825737 | uncertain significance | Alstrom syndrome | 2022-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 630 of the ALMS1 protein (p.Gly630Asp). This variant is present in population databases (rs531859344, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ALMS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 575048). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
Johns Hopkins Genomics, |
RCV000697141 | SCV001548515 | uncertain significance | Alstrom syndrome | 2021-03-22 | criteria provided, single submitter | clinical testing | ALMS1 c.1883G>A (rs531859344) is rare (<0.1%) in a large population dataset (gnomAD: 5/280468 total alleles; 0.0018%; no homozygotes). This ALMS1 variant has not been reported in the literature to our knowledge, but there is an entry for this variant in ClinVar (Variation ID: 575048). Of three bioinformatics tools queried, one predicts that the substitution would be possibly damaging, while two predict that it would be tolerated. The glycine residue at this position is not highly evolutionarily conserved among the species assessed. Due to insufficient evidence, we consider the clinical significance of c.1883G>A to be uncertain at this time. |
Ambry Genetics | RCV002406602 | SCV002717389 | uncertain significance | Cardiovascular phenotype | 2022-10-06 | criteria provided, single submitter | clinical testing | The p.G630D variant (also known as c.1889G>A), located in coding exon 8 of the ALMS1 gene, results from a G to A substitution at nucleotide position 1889. The glycine at codon 630 is replaced by aspartic acid, 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. |
Fulgent Genetics, |
RCV000697141 | SCV002794081 | uncertain significance | Alstrom syndrome | 2021-12-23 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003442039 | SCV004167996 | uncertain significance | not provided | 2023-04-26 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Natera, |
RCV000697141 | SCV002080435 | uncertain significance | Alstrom syndrome | 2021-10-06 | no assertion criteria provided | clinical testing |