Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Personalized Diabetes Medicine Program, |
RCV001172504 | SCV001335557 | likely benign | Monogenic diabetes | 2019-02-22 | criteria provided, single submitter | research | ACMG criteria: BP4 (REVEL 0.085 + 5 predictors), BP1 = likely benign |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001328464 | SCV001519611 | uncertain significance | not specified | 2021-03-11 | criteria provided, single submitter | clinical testing | Variant summary: ALMS1 c.12100G>A (p.Ala4034Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 249478 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.12100G>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 and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Invitae | RCV001833728 | SCV002162039 | uncertain significance | Alstrom syndrome | 2022-06-23 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 4036 of the ALMS1 protein (p.Ala4036Thr). This variant is present in population databases (rs757364858, gnomAD 0.01%). 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: 916711). 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. |
Clinical Genomics, |
RCV001833728 | SCV003928180 | likely risk allele | Alstrom syndrome | criteria provided, single submitter | research | Potent mutations in ALMS1 are associated with a rare condition called Alstrom syndrome. It can cause excessive eating, insulin resistance. However, no evidence is found to ascertain the role of rs757364858 in Alstrom syndrome yet. | |
Natera, |
RCV001833728 | SCV002079052 | uncertain significance | Alstrom syndrome | 2021-07-21 | no assertion criteria provided | clinical testing |