Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC related information was provided by the message!
  • No CSPEC computed assertion could be determined for this classification!
  • See Evidence submitted by expert panel for details.

Variant: NM_004958.3(MTOR):c.5930C>A (p.Thr1977Lys)

CA248390

156702 (ClinVar)

Gene: MTOR
Condition: cerebral malformation
Inheritance Mode: Autosomal dominant inheritance (mosaic)
Link to MONDO
UUID: 9187950f-2c32-459c-b678-3bd146dec7ec
Approved on: 2021-01-31
Published on: 2021-09-27

HGVS expressions

NM_004958.3:c.5930C>A
NM_004958.3(MTOR):c.5930C>A (p.Thr1977Lys)
NC_000001.11:g.11128107G>T
CM000663.2:g.11128107G>T
NC_000001.10:g.11188164G>T
CM000663.1:g.11188164G>T
NC_000001.9:g.11110751G>T
NG_033239.1:g.139445C>A
ENST00000703118.1:c.*1305C>A
ENST00000703131.1:n.1734C>A
ENST00000703139.1:c.567C>A
ENST00000703140.1:c.5717C>A
ENST00000703141.1:c.*1250C>A
ENST00000703142.1:c.*2760C>A
ENST00000361445.9:c.5930C>A
ENST00000361445.8:c.5930C>A
ENST00000376838.5:c.545C>A
NM_004958.4:c.5930C>A
NM_001386500.1:c.5930C>A
NM_001386501.1:c.4682C>A
More

Pathogenic

Met criteria codes 6
PM2 PS4 PS2_Moderate PP2 PS3_Supporting PM1_Supporting
Not Met criteria codes 20
PM3 PM5 PM4 BA1 PM6 PS1 PP1 PP3 PP4 PVS1 BS2 BS1 BS4 BS3 BP4 BP3 BP1 BP2 BP5 BP7

Evidence Links 3

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Brain Malformations VCEP
The c.5930C>A p.T1977R missense variant in the MTOR gene is previously reported in the literature and has been classified as PATHOGENIC. Testing of unaffected and affected tissue show variable allelic fractions consistent with a post-zygotic event (PMID: 25799227) (PS2_Moderate). This variant has been shown to significantly increase phosphorylation levels in experiments with case and controls cells of similar isogenic backgrounds (PMID: 24631838) (PS3_supporting). This variant has been identified in 2 individuals with neuropathology confirmatory of a malformation of cortical development, 1 individual with neuroimaging appearance consistent with a malformation of cortical development (without neuropathology), 5 tumor samples in the literature and COSMIC (PMID: 25799227, PMID: 29281825) (PS4_Strong). This variant is located in the MTOR kinase domain(PM1). This variant is absent from the Genome Aggregation Database (http://gnomad.broadinstitute.org) (PM2). This gene has a low rate of benign missense changes (PP2).
Met criteria codes
PM2
absent from gnomAD
PS4
5 tumor samples in COSMIC
FCD-14 PubMed:29281825
FCD116 & FCD145 PubMed:25799227
PS2_Moderate
FCD145 1.5% in brain, absent from saliva PubMed:25799227
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3_Supporting
AKT phosphrylation PubMed:24631838
PM1_Supporting
kinase domain
Not Met criteria codes
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
FCD145 1.5% in brain, absent from saliva PubMed:25799227
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PVS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP7
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.