Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000523193 | SCV000618740 | uncertain significance | not provided | 2023-03-08 | 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 |
| Invitae | RCV001242906 | SCV001416026 | uncertain significance | Alstrom syndrome | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 3753 of the ALMS1 protein (p.Asn3753Ser). This variant is present in population databases (rs199917289, 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: 450189). 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, |
RCV001328364 | SCV001519474 | uncertain significance | not specified | 2021-03-15 | criteria provided, single submitter | clinical testing | Variant summary: ALMS1 c.11252A>G (p.Asn3751Ser; also known as c.11258A>G) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00015 in 279478 control chromosomes, predominantly at a frequency of 0.0017 within the African or African-American subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in ALMS1 causing Alstrom Syndrome with Dilated Cardiomyopathy (0.00015 vs 0.0018), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.11252A>G in individuals affected with Alstrom Syndrome with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002438254 | SCV002753287 | likely benign | Cardiovascular phenotype | 2021-05-25 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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, |
RCV001242906 | SCV002781418 | uncertain significance | Alstrom syndrome | 2022-05-06 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV001242906 | SCV004562662 | uncertain significance | Alstrom syndrome | 2023-11-06 | criteria provided, single submitter | clinical testing | The ALMS2 c.11255A>G; p.Asn3752Ser variant (rs199917289), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 450189). This variant is found in the African population with an allele frequency of 0.17% (42/24,134 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is neutral (REVEL: 0.045). Given the lack of clinical and functional data, the significance of the p.Asn3752Ser variant is uncertain at this time. |
| Natera, |
RCV001242906 | SCV002079000 | uncertain significance | Alstrom syndrome | 2021-06-30 | no assertion criteria provided | clinical testing |