Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000133227 | SCV000193640 | likely benign | not specified | 2015-04-10 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000133227 | SCV000310762 | likely benign | not specified | criteria provided, single submitter | clinical testing | ||
Invitae | RCV001085738 | SCV000645676 | benign | Severe neonatal-onset encephalopathy with microcephaly | 2024-01-24 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV000712284 | SCV000842735 | benign | not provided | 2017-12-20 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000719501 | SCV000850368 | likely benign | History of neurodevelopmental disorder | 2016-02-08 | 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000133227 | SCV001362254 | benign | not specified | 2019-02-15 | criteria provided, single submitter | clinical testing | Variant summary: The variant, MECP2 c.753C>T results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00015 in 199952 control chromosomes (14 hemizygotes), predominantly at a frequency of 0.00051 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 61-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in MECP2 causing Rett Syndrome phenotype (8.3e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. The variant, c.753C>T has been reported in the literature in individuals affected with Rett Syndrome (Chae_2004, Petel-Galil_2006, Temudo_2009, Hadzsiev_2011). However, these reports do not provide unequivocal conclusions about association of the variant with Rett Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign. |
Gene |
RCV000712284 | SCV001941763 | benign | not provided | 2015-03-03 | criteria provided, single submitter | clinical testing | |
Rett |
RCV000133227 | SCV000188227 | benign | not specified | 2011-11-01 | no assertion criteria provided | curation |