Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001836914 | SCV001949952 | likely benign | Overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes | 2022-02-12 | reviewed by expert panel | curation | The c.5501C>T (NM_004958.4) variant in MTOR is a missense variant predicted to cause substitution of (p.Thr1834Met). The highest population minor allele frequency in gnomAD v2.1.1 is 0.0006661 in European (non Finnish) population, which is higher than the ClinGen BMEP threshold ([>0.00037]) for BS1, and therefore meets this criterion (BS1). MTOR, in which the variant was identified, is defined by the ClinGen Brain Malformations Expert Panel as a gene that has a low rate of benign missense variation and where pathogenic missense variants are a common mechanism of disease (PP2). This variant resides within the focal adhesion kinase domain of MTOR that is defined as a critical functional domain by the ClinGen BMEP (PMIDs: 23322780, 27482884, 21210909) (PM1_Supporting). In summary, this variant meets the criteria to be classified as Likely benign for mosaic autosomal dominant overgrowth with or without cerebral malformations due to abnormalities in MTOR-pathway genes based on the ACMG/AMP criteria applied, as specified by the ClinGen Brain Malformations Expert Panel: BS1, PP2, PM1_P; -2 points (VCEP specifications version 1; Approved: 1/31/2021) |
Labcorp Genetics |
RCV000861765 | SCV001002162 | benign | not provided | 2024-01-30 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000861765 | SCV001501876 | likely benign | not provided | 2024-04-01 | criteria provided, single submitter | clinical testing | MTOR: BP4, BS2 |
Gene |
RCV000861765 | SCV001846022 | benign | not provided | 2019-07-10 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV001816928 | SCV002066998 | likely benign | not specified | 2019-12-02 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002536229 | SCV003537186 | likely benign | Inborn genetic diseases | 2021-07-19 | 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. |
Breakthrough Genomics, |
RCV000861765 | SCV005263227 | likely benign | not provided | criteria provided, single submitter | not provided | ||
Prevention |
RCV003928337 | SCV004740933 | likely benign | MTOR-related disorder | 2022-05-10 | 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). |