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]
Link to SEPIO compliant JSON-LD document
  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.
  • See Evidence submitted by expert panel for details.

Variant: NM_004958.3:c.5432G>T

CA338398676

664963 (ClinVar)

Gene: MTOR
Condition: overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
Inheritance Mode: Autosomal dominant inheritance (mosaic)
Link to MONDO
UUID: 2991ffb3-a1ae-49f8-a7c6-68b739d0c562

HGVS expressions

NM_004958.3:c.5432G>T
NC_000001.11:g.11130710C>A
CM000663.2:g.11130710C>A
NC_000001.10:g.11190767C>A
CM000663.1:g.11190767C>A
NC_000001.9:g.11113354C>A
NG_033239.1:g.136842G>T
ENST00000361445.9:c.5432G>T
ENST00000361445.8:c.5432G>T
ENST00000376838.5:c.47G>T
NM_004958.4:c.5432G>T
NM_001386500.1:c.5432G>T
NM_001386501.1:c.4184G>T
NM_004958.4(MTOR):c.5432G>T (p.Arg1811Leu)

Uncertain Significance

Met criteria codes 3
PM2_Supporting PP2 PM1_Supporting
Not Met criteria codes 23
PS2 PS4 PS3 PS1 PP4 PP1 PP3 PM3 PM4 PM5 PM6 BA1 BS2 PVS1 BS4 BS3 BS1 BP2 BP3 BP4 BP1 BP5 BP7

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Brain Malformations VCEP
The c.5432G>T (NM_004958.4) variant in MTOR is a missense variant predicted to cause substitution of (p.Arg1811Leu). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). 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 targeting 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 Uncertain significance 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: PM2_P, PP2, PM1_P; 3 points (VCEP specifications version 1; Approved: 1/31/2021)
Met criteria codes
PM2_Supporting
Present in 1/31236 (0.003&) Latino alleles in gnomAD
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1_Supporting
kinase domain
Not Met criteria codes
PS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS4
no tumors present in COSMIC
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
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
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
PM3
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
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM6
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
BS2
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
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
BS1
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
BP3
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
BP1
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
Approved on: 2022-02-11
Published on: 2022-02-11
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