Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000193703 | SCV000190994 | likely benign | not specified | 2016-06-30 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Genetic Services Laboratory, |
RCV000193703 | SCV000247930 | likely benign | not specified | 2014-03-06 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000465490 | SCV000556732 | likely benign | Severe neonatal-onset encephalopathy with microcephaly | 2024-09-27 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000193703 | SCV005039464 | likely benign | not specified | 2024-03-12 | criteria provided, single submitter | clinical testing | Variant summary: MECP2 c.1154C>A (p.Pro385His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5e-05 in 1199903 control chromosomes and 18 hemizygotes (gnomAD database v4.0.0). The observed variant frequency is approximately 6 fold of 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 benign. To our knowledge, no occurrence of c.1154C>A in individuals affected with Rett Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 156631). Based on the evidence outlined above, the variant was classified as likely benign. |
Ambry Genetics | RCV004948195 | SCV005448953 | likely benign | Inborn genetic diseases | 2024-10-09 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |
Prevention |
RCV004532629 | SCV004744685 | likely benign | MECP2-related disorder | 2022-03-24 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |