Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001060657 | SCV001225361 | likely pathogenic | Alstrom syndrome | 2019-09-25 | criteria provided, single submitter | clinical testing | This variant is a deletion of part of exon 12 (c.9785-1270_9861delinsTC) of the ALMS1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with ALMS1-related conditions. Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001060657 | SCV002600448 | likely pathogenic | Alstrom syndrome | 2022-10-11 | criteria provided, single submitter | clinical testing | Variant summary: ALMS1 c.9779-1269_9856del1347 (also known as c.9785-1269_9862del1347 in RefSeq) is a large deletion of part of exon 12 involving a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. The variant was absent in 21694 control chromosomes (gnomAD, Structural Variant dataset). To our knowledge, no occurrence of c.9779-1269_9856del1347 in individuals affected with Alstrom Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted a clinical-significance assessment for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |