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 computer assertion could be determined for this classification!

Variant: NM_001165963.4:c.2792G>A

CA303154

189869 (ClinVar)

Gene: SCN1A
Condition: Dravet syndrome
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: c2be7fc0-7687-44e5-b052-6fc0474ee698
Approved on: 2024-05-09
Published on: 2024-05-09

HGVS expressions

NM_001165963.4:c.2792G>A
NC_000002.12:g.166037930C>T
CM000664.2:g.166037930C>T
NC_000002.11:g.166894440C>T
CM000664.1:g.166894440C>T
NC_000002.10:g.166602686C>T
NG_011906.1:g.40710G>A
ENST00000689288.1:c.*828G>A
ENST00000303395.9:c.2792G>A
ENST00000635750.1:c.2759G>A
ENST00000635776.1:c.2759G>A
ENST00000636194.1:c.*285G>A
ENST00000636759.1:c.*2582G>A
ENST00000637968.1:n.3044G>A
ENST00000637988.1:c.2759G>A
ENST00000640036.1:c.2759G>A
ENST00000641575.1:c.2756G>A
ENST00000641603.1:c.2792G>A
ENST00000641996.1:c.*2346G>A
ENST00000671940.1:c.*735G>A
ENST00000673490.1:n.5265G>A
ENST00000674923.1:c.2792G>A
ENST00000303395.8:c.2792G>A
ENST00000375405.7:c.2759G>A
ENST00000409050.1:c.2708G>A
ENST00000423058.6:c.2792G>A
NM_001165963.1:c.2792G>A
NM_001165964.1:c.2708G>A
NM_001202435.1:c.2792G>A
NM_006920.4:c.2759G>A
NM_001165963.2:c.2792G>A
NM_001165964.2:c.2708G>A
NM_001202435.2:c.2792G>A
NM_001353948.1:c.2792G>A
NM_001353949.1:c.2759G>A
NM_001353950.1:c.2759G>A
NM_001353951.1:c.2759G>A
NM_001353952.1:c.2759G>A
NM_001353954.1:c.2756G>A
NM_001353955.1:c.2756G>A
NM_001353957.1:c.2708G>A
NM_001353958.1:c.2708G>A
NM_001353960.1:c.2705G>A
NM_001353961.1:c.350G>A
NM_006920.5:c.2759G>A
NR_148667.1:n.3164G>A
NM_001165963.3:c.2792G>A
NM_001165964.3:c.2708G>A
NM_001202435.3:c.2792G>A
NM_001353948.2:c.2792G>A
NM_001353949.2:c.2759G>A
NM_001353950.2:c.2759G>A
NM_001353951.2:c.2759G>A
NM_001353952.2:c.2759G>A
NM_001353954.2:c.2756G>A
NM_001353955.2:c.2756G>A
NM_001353957.2:c.2708G>A
NM_001353958.2:c.2708G>A
NM_001353960.2:c.2705G>A
NM_001353961.2:c.350G>A
NM_006920.6:c.2759G>A
NR_148667.2:n.3145G>A
More

Pathogenic

Met criteria codes 4
PM2_Supporting PP3_Moderate PM6_Strong PS4
Not Met criteria codes 4
BS1 BP4 BA1 PM1

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.2792G>A variant in SCN1A is a missense variant predicted to cause substitution of arginine by histidine at amino acid 931 (p.Arg931His). The variant has been identified as a de novo occurrence with unconfirmed parental relationships in at least 2 individual(s) with Dravet syndrome (PMIDs: 28079314, 35072530) (PM6_Strong), and in at least 3 unrelated individuals with Dravet syndrome with unknown inheritance (PMIDs: 21719429, 31031587, 33067208) (PS4), with additional evidence available in the literature. The variant is absent from gnomAD v2.1.1 (PM2_Supporting). The computational predictor REVEL gives a score of 0.966, which is above the threshold of 0.773, evidence that correlates with a maximum strength of PP3_Moderate. In summary, this variant meets the criteria to be classified as pathogenic for autosomal dominant Dravet syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen Epilepsy Sodium Channel VCEP: PM6_Strong, PS4, PM2_Supporting, PP3_Moderate. (version 1; approved August 4, 2023).
Met criteria codes
PM2_Supporting
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PP3_Moderate
The computational predictor REVEL gives a score of 0.966, which is above the threshold of 0.773, evidence that correlates with a maximum strength of PP3_Moderate.
PM6_Strong
This variant was identified, presumed de novo, in at least 2 individuals with Dravet syndrome in the published literature.
PS4
This variant has been reported in at least 3 individuals with Dravet syndrome in the published literature.
Not Met criteria codes
BS1
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
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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