Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000473735 | SCV000431896 | uncertain significance | Alstrom syndrome | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194012 | SCV001363241 | benign | not specified | 2019-11-25 | criteria provided, single submitter | clinical testing | Variant summary: The ALMS1 variant, c.66_74dupGGAGGAGGA (p.Glu26_Glu28dup, also known as c.69_77dup) is located in a Glu repetitive region. The variant allele was found at a frequency of 0.0043 in 83366 control chromosomes, predominantly at a frequency of 0.011 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 5-folds over the estimated maximal expected allele frequency for a pathogenic variant in ALMS1 causing Cardiomyopathy phenotype (0.0022), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.66_74dupGGAGGAGGA in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. |
Ambry Genetics | RCV002374820 | SCV002667649 | benign | Cardiovascular phenotype | 2019-01-09 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |