Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003448328 | SCV004175921 | likely benign | Rett syndrome | 2023-12-06 | reviewed by expert panel | curation | The p.Leu383Phe variant in MECP2 (NM_004992.4) is observed in at least 2 unaffected individuals (internal database - Invitae) (BS2). This variant is also found in two patients with an alternate molecular basis of disease (internal database - GeneDx) (BP5). The p.Leu383Phe variant is present in 10 XX and 5 XY individuals in gnomAD v4 (0.001%) (not sufficient to meet BS1 criteria). Computational prediction analysis tools are inconclusive for this variant. In summary, the p.Leu395Phe variant in MECP2 is classified as Likely Benign based on the ACMG/AMP criteria (BS2, BP5). |
Gene |
RCV000600874 | SCV000728725 | likely benign | not specified | 2017-03-14 | 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000600874 | SCV000919618 | uncertain significance | not specified | 2023-03-14 | criteria provided, single submitter | clinical testing | Variant summary: MECP2 c.1147C>T (p.Leu383Phe) 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 5.8e-06 in 173283 control chromosomes including one female in the gnomAD database. 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.1147C>T in individuals affected with Rett Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign (n=2) and VUS (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Invitae | RCV001210472 | SCV001381961 | likely benign | Severe neonatal-onset encephalopathy with microcephaly | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV001508974 | SCV001715429 | uncertain significance | not provided | 2020-12-08 | criteria provided, single submitter | clinical testing |