Genetic Information
Gene & Transcript Details
Gene
MLH1
Transcript
NM_000249.4
MANE Select
Total Exons
—
Reference Sequence
NC_000003.11
Alternative Transcripts
| ID | Status | Details |
|---|---|---|
| NM_000249.4 | MANE Select | 2494 nt | 31–2301 |
| NM_000249.3 | RefSeq Select | 2662 nt | 199–2469 |
| NM_000249.2 | Alternative | 2524 nt | 61–2331 |
Variant Details
HGVS Notation
NM_000249.4:c.1515T>C
Protein Change
S505=
Location
Exon 13
(Exon 13 of )
13
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers
—
Clinical & Population Data
Population Frequency
gnomAD Global Frequency
0.00199 in 100,000
Extremely Rare
ACMG Criteria Applied
PM2
This variant is absent or extremely rare in population databases (PM2 criteria applies).
ClinVar
OpenClassification
Likely Benign
3 publications
Clinical Statement
"This variant has been reported in ClinVar as Likely benign (5 clinical laboratories) and as Likely Benign (1 clinical laboratories) and as Benign (1 clinical laboratories)."
COSMIC Somatic Evidence
OpenCOSMIC ID
Recurrence
0 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
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Functional Impact & Domains
Functional Domain
Hotspot Status
Not a hotspot
Domain Summary
This variant is not located in a mutational hotspot or critical domain.
Related Variants in This Domain
No evidence of other pathogenic variants at this position in gene MLH1.
Functional Summary
Error in OpenAI Consolidation. OncoKB: MLH1S505=MLH1S505=SomaticNCBI Gene:4292|Show additional gene information Variant OverviewMLH1, a DNA mismatch repair protein, is recurrently altered by deletion and mutation in various cancer types.This is a synonymous mutation and is not annotated by OncoKB. JAX-CKB: No results found
Database Previews
OncoKB
JAX-CKB
Click on previews to view full database entries. External databases may require institutional access.
Computational Analysis
Pathogenicity Predictions
SpliceAIPredictor Consensus
Mixed/VUS
PP3 Applied
No
REVEL Score
0.0
Threshold: ≥0.75 = PP3 applied
SpliceAI Scores
Window: ±500bp| Effect Type | Score | Position |
|---|---|---|
| Acceptor Loss (AL) | 0.0 | 16 bp |
| Donor Loss (DL) | 0.0 | -35 bp |
| Acceptor Gain (AG) | 0.0 | -105 bp |
| Donor Gain (DG) | 0.0 | 43 bp |
High impact (≥0.5)
Medium impact (0.2-0.49)
Low impact (<0.2)
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific)
Filter Criteria:
PM2
PM2 (Unknown (Pre-LLM))
From pre-LLM assessment (LLM Failed)
BP4
BP4 (Unknown (Pre-LLM))
From pre-LLM assessment (LLM Failed)
BP6
BP6 (Unknown (Pre-LLM))
From pre-LLM assessment (LLM Failed)