Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000673152 | SCV000798323 | likely pathogenic | Alstrom syndrome | 2018-03-09 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000673152 | SCV001583952 | pathogenic | Alstrom syndrome | 2020-09-13 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). This variant has been observed in individual(s) with Alstrom syndrome (PMID: 25846608). It is also known as c.8150_8151insT in the literature. ClinVar contains an entry for this variant (Variation ID: 557063). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser2719Phefs*7) in the ALMS1 gene. It is expected to result in an absent or disrupted protein product. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000673152 | SCV002766381 | pathogenic | Alstrom syndrome | 2022-11-16 | criteria provided, single submitter | clinical testing | Variant summary: ALMS1 c.8149dupT (p.Ser2717PhefsX7, also known as c.8155dupT/p.Ser2719PhefsX7) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 249554 control chromosomes. c.8149dupT has been reported in the literature in individuals affected with Alstrom Syndrome (Marshall_2015). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |