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 computed assertion could be determined for this classification!

Variant: NM_001165963.4(SCN1A):c.2941C>A (p.Leu981Ile)

CA16042438

372977 (ClinVar)

Gene: SCN1A
Condition: generalized epilepsy with febrile seizures plus
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 33cd32a2-37e3-4d92-abfb-c7cb654ae1bc
Approved on: 2024-07-30
Published on: 2024-11-05

HGVS expressions

NM_001165963.4:c.2941C>A
NM_001165963.4(SCN1A):c.2941C>A (p.Leu981Ile)
NC_000002.12:g.166037781G>T
CM000664.2:g.166037781G>T
NC_000002.11:g.166894291G>T
CM000664.1:g.166894291G>T
NC_000002.10:g.166602537G>T
NG_011906.1:g.40859C>A
ENST00000689288.1:c.*977C>A
ENST00000303395.9:c.2941C>A
ENST00000635750.1:c.2908C>A
ENST00000635776.1:c.2908C>A
ENST00000636194.1:c.*434C>A
ENST00000636759.1:c.*2731C>A
ENST00000637968.1:n.3193C>A
ENST00000637988.1:c.2908C>A
ENST00000640036.1:c.2908C>A
ENST00000641575.1:c.2905C>A
ENST00000641603.1:c.2941C>A
ENST00000641996.1:c.*2495C>A
ENST00000671940.1:c.*884C>A
ENST00000673490.1:n.5414C>A
ENST00000674923.1:c.2941C>A
ENST00000303395.8:c.2941C>A
ENST00000375405.7:c.2908C>A
ENST00000409050.1:c.2857C>A
ENST00000423058.6:c.2941C>A
NM_001165963.1:c.2941C>A
NM_001165964.1:c.2857C>A
NM_001202435.1:c.2941C>A
NM_006920.4:c.2908C>A
NM_001165963.2:c.2941C>A
NM_001165964.2:c.2857C>A
NM_001202435.2:c.2941C>A
NM_001353948.1:c.2941C>A
NM_001353949.1:c.2908C>A
NM_001353950.1:c.2908C>A
NM_001353951.1:c.2908C>A
NM_001353952.1:c.2908C>A
NM_001353954.1:c.2905C>A
NM_001353955.1:c.2905C>A
NM_001353957.1:c.2857C>A
NM_001353958.1:c.2857C>A
NM_001353960.1:c.2854C>A
NM_001353961.1:c.499C>A
NM_006920.5:c.2908C>A
NR_148667.1:n.3313C>A
NM_001165963.3:c.2941C>A
NM_001165964.3:c.2857C>A
NM_001202435.3:c.2941C>A
NM_001353948.2:c.2941C>A
NM_001353949.2:c.2908C>A
NM_001353950.2:c.2908C>A
NM_001353951.2:c.2908C>A
NM_001353952.2:c.2908C>A
NM_001353954.2:c.2905C>A
NM_001353955.2:c.2905C>A
NM_001353957.2:c.2857C>A
NM_001353958.2:c.2857C>A
NM_001353960.2:c.2854C>A
NM_001353961.2:c.499C>A
NM_006920.6:c.2908C>A
NR_148667.2:n.3294C>A
More

Uncertain Significance

Met criteria codes 2
PP3_Moderate PM2_Supporting
Not Met criteria codes 24
BS2 BS3 BS4 BS1 BP7 BP5 BP3 BP4 BP1 BP2 PS1 PS3 PS2 PS4 PP2 PP4 PP1 PM5 PM1 PM4 PM3 PM6 PVS1 BA1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Epilepsy Sodium Channel Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for SCN1A Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Epilepsy Sodium Channel VCEP
The c.2941C>A variant in SCN1A is a missense variant predicted to cause substitution of leucine by isoleucine at amino acid 981 (p.Leu981Ile). This variant has not been reported in the published literature to date. The variant is absent in gnomAD (v2.1.1) (PM2_supporting). The computational predictor REVEL gives a score of 0.843 (PP3). Another missense variant (c.2942T>C (p.Leu981Pro) in the same codon of the same gene has been reported in a patient with Dravet syndrome (PMIDs: 28012175). However, this variant has not yet met the criteria to be classified as pathogenic or likely pathogenic by ClinGen (Epilepsy Sodium Channel VCEP). In summary, this variant meets the criteria to be classified as Variant of Uncertain Significance for autosomal dominant SCN1A-related disorder, based on the ACMG/AMP criteria applied, as specified by the ClinGen Epilepsy Sodium Channel VCEP: PM2_supporting, PP3 (version 1.0, approved July 23, 2024).
Met criteria codes
PP3_Moderate
REVEL score = 0.843
PM2_Supporting
Variant is absent in controls in gnomAD
Not Met criteria codes
BS2
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
BS4
N/A
BS1
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
BP5
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
N/A
BP2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS1
variant at corresponding position: SCN2A:p.Leu972Ile - classified as a VUS in ClinVar (Invitae), no publications found
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS2
This variant has not been reported in the literature in affected individuals.
PS4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP2
N/A
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
PM5
Variation ID: 2203193, SCN1A:c.2942T>C (p.Leu981Pro) - reported as pathogenic in ClinVar (Invitae), reported in individual with Dravet syndrome, de novo, maternity/paternity not confirmed, only SCN1A analyzed (PMID: 28012175) (PM6), absent in controls (PM2_supporting), REVEL 0.986 (PP3_moderate) - classifies to VUS based on new criteria; variant at corresponding position: SCN8A:p.Leu966Trp - VUS in ClinVar (Invitae), no publications found
PM1
Not located in Pathogenic Enriched Region (PER)
PM4
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM3
N/A
PM6
This variant has not been reported in the literature in affected individuals.
PVS1
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
Curation History
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