Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000418543 | SCV000533094 | uncertain significance | not provided | 2024-09-04 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
Labcorp Genetics |
RCV000560896 | SCV000631775 | uncertain significance | Alstrom syndrome | 2022-10-24 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1098 of the ALMS1 protein (p.Tyr1098Cys). This variant is present in population databases (rs201816596, gnomAD 0.2%). 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: 390302). 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. |
Genetic Services Laboratory, |
RCV001821206 | SCV002070952 | uncertain significance | not specified | 2021-06-22 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the ALMS1 gene demonstrated a sequence change, c.3293A>G, in exon 8 that results in an amino acid change, p.Tyr1098Cys. This sequence change has been described in the gnomAD database with a frequency of 0.19% in the African/African-American subpopulation (dbSNP rs201816596). The p.Tyr1098Cys change affects a moderately conserved amino acid residue located in a domain of the ALMS1 protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Tyr1098Cys substitution. This sequence change does not appear to have been previously described in patients with ALMS1-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Tyr1098Cys change remains unknown at this time. |
Ambry Genetics | RCV002323649 | SCV002606972 | likely benign | Cardiovascular phenotype | 2021-07-26 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Fulgent Genetics, |
RCV000560896 | SCV002789646 | uncertain significance | Alstrom syndrome | 2022-03-04 | criteria provided, single submitter | clinical testing | |
New York Genome Center | RCV000560896 | SCV003925067 | uncertain significance | Alstrom syndrome | 2020-12-09 | criteria provided, single submitter | clinical testing | |
Breakthrough Genomics, |
RCV000418543 | SCV005187747 | uncertain significance | not provided | criteria provided, single submitter | not provided | ||
Natera, |
RCV000560896 | SCV001458920 | uncertain significance | Alstrom syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |