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
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  • See Evidence submitted by expert panel for details.

Variant: NM_004958.4(MTOR):c.6752G>A (p.Arg2251Gln)

CA338385973

858694 (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: 4d2d54ba-e139-4caa-bb42-fde58e1dc0dd
Approved on: 2021-08-06
Published on: 2021-09-27

HGVS expressions

NM_004958.4:c.6752G>A
NM_004958.4(MTOR):c.6752G>A (p.Arg2251Gln)
NC_000001.11:g.11122037C>T
CM000663.2:g.11122037C>T
NC_000001.10:g.11182094C>T
CM000663.1:g.11182094C>T
NC_000001.9:g.11104681C>T
NG_033239.1:g.145515G>A
ENST00000703118.1:c.*2127G>A
ENST00000703131.1:n.2753G>A
ENST00000703139.1:c.1389G>A
ENST00000703140.1:c.6539G>A
ENST00000703141.1:c.*2269G>A
ENST00000703142.1:c.*3582G>A
ENST00000361445.9:c.6752G>A
ENST00000361445.8:c.6752G>A
ENST00000376838.5:c.1367G>A
NM_004958.3:c.6752G>A
NM_001386500.1:c.6752G>A
NM_001386501.1:c.5504G>A
More

Uncertain Significance

Met criteria codes 1
PP2
Not Met criteria codes 5
BS1 PM2 PM1 PM5 BA1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
Evidence submitted by expert panel
Brain Malformations VCEP
The c.6752G>A (NM_004958.4) variant in MTOR is a missense variant predicted to cause substitution of (p.Arg2251Gln). 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). 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: PP2; 1 point (VCEP specifications version 1; Approved: 1/31/2021)
Met criteria codes
PP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Not Met criteria codes
BS1
Present in 1 individual in "Other" subpopulation (0.048% (1/2088)) in gnomAD v3. (The allele frequency meets criteria for BS1 but also PM2 based on a single occurrence so neither point is awarded).
PM2
Present in 1 individual in "Other" subpopulation (0.048% (1/2088)) in gnomAD v3. (The allele frequency meets criteria for BS1 but also PM2 based on a single occurrence so neither point is awarded).
PM1
Not in established functional domains for MTOR
PM5
Different missense change is present in ClinVar with R2251W but it is listed as a VUS.
BA1
Present in 1 individual in "Other" subpopulation (0.048% (1/2088)) in gnomAD v3.
Curation History
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