Genetic Information

Gene & Transcript Details

Gene
KIT
Transcript
NM_000222.2 MANE Select
Total Exons
Reference Sequence
NC_000004.11
Alternative Transcripts
IDStatusDetails
NM_000222.3 MANE Select 5147 nt | 59–2989
NM_000222.2 RefSeq Select 5190 nt | 88–3018
NM_000222.1 Alternative 5084 nt | 22–2952

Variant Details

HGVS Notation
NM_000222.2:c.1351T>C
Protein Change
S451P
Location
Exon 9 (Exon 9 of )
9
5'Exon Structure3'
Functional Consequence
Loss of Function
Alternate Identifiers

Clinical & Population Data

Population Frequency

gnomAD
Global Frequency
0.00213 in 100,000
Extremely Rare
ACMG Criteria Applied PM2
This variant is absent or extremely rare in population databases (PM2 criteria applies).

ClinVar

Open
Classification
Uncertain Significance (VUS)
2 publications
Publications List
PMID: 29641532

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.

Clinical Statement

"This variant has been reported in ClinVar as Uncertain significance (4 clinical laboratories) and as Likely benign (1 clinical laboratories)."

COSMIC Somatic Evidence

Open
COSMIC ID
Recurrence
0 occurrences
PM1 Criteria
Not Applied
COSMIC Database Preview
COSMIC 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 KIT.

Functional Studies & Therapeutic Relevance

Functional Summary

The KIT S451P variant has not been functionally characterized, and its biological significance remains unknown.

Database Previews
OncoKB
OncoKB Preview
JAX-CKB
JAX-CKB Preview

Click on previews to view full database entries. External databases may require institutional access.

Computational Analysis

Pathogenicity Predictions

SpliceAI
Predictor Consensus
Mixed/VUS
PP3 Applied
No
REVEL Score
0.035
Threshold: ≥0.75 = PP3 applied

SpliceAI Scores

Window: ±500bp
Effect Type Score Position
- Acceptor Loss (AL) 0.0 19 bp
- Donor Loss (DL) 0.0 189 bp
+ Acceptor Gain (AG) 0.0 -4 bp
+ Donor Gain (DG) 0.0 120 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)