Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000553360 | SCV000631766 | uncertain significance | Alstrom syndrome | 2022-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with asparagine, which is neutral and polar, at codon 475 of the ALMS1 protein (p.His475Asn). This variant is present in population databases (rs200454461, gnomAD 0.05%). 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: 459855). 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001293477 | SCV001482055 | uncertain significance | not specified | 2021-02-01 | criteria provided, single submitter | clinical testing | Variant summary: ALMS1 c.1420C>A (p.His474Asn) results in a conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 249078 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in ALMS1 causing Alstrom Syndrome With Dilated Cardiomyopathy (6e-05 vs 0.0018), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1420C>A in individuals affected with Alstrom Syndrome With Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Genome- |
RCV000553360 | SCV001716374 | uncertain significance | Alstrom syndrome | 2021-05-18 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001553245 | SCV001774075 | uncertain significance | not provided | 2022-07-23 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002395334 | SCV002702698 | uncertain significance | Cardiovascular phenotype | 2023-08-08 | criteria provided, single submitter | clinical testing | The p.H475N variant (also known as c.1423C>A), located in coding exon 7 of the ALMS1 gene, results from a C to A substitution at nucleotide position 1423. The histidine at codon 475 is replaced by asparagine, an amino acid with similar properties. This amino acid position is not well 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, |
RCV000553360 | SCV002815202 | uncertain significance | Alstrom syndrome | 2022-02-04 | criteria provided, single submitter | clinical testing |