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.1170+5G>C

CA16603947

393000 (ClinVar)

Gene: SCN1A
Condition: complex neurodevelopmental disorder
Inheritance Mode: Autosomal dominant inheritance
UUID: 4c546bba-96a7-4f6b-abb9-8fca75864f83
Approved on: 2024-10-01
Published on: 2024-11-05

HGVS expressions

NM_001165963.4:c.1170+5G>C
NM_001165963.4(SCN1A):c.1170+5G>C
NC_000002.12:g.166047622C>G
CM000664.2:g.166047622C>G
NC_000002.11:g.166904132C>G
CM000664.1:g.166904132C>G
NC_000002.10:g.166612378C>G
NG_011906.1:g.31018G>C
ENST00000689288.1:c.1170+5G>C
ENST00000303395.9:c.1170+5G>C
ENST00000635750.1:c.1170+5G>C
ENST00000635776.1:c.1170+5G>C
ENST00000636194.1:c.1170+5G>C
ENST00000636759.1:c.*960+5G>C
ENST00000637968.1:n.1422+5G>C
ENST00000637988.1:c.1170+5G>C
ENST00000640036.1:c.1170+5G>C
ENST00000641575.1:c.1170+5G>C
ENST00000641603.1:c.1170+5G>C
ENST00000641996.1:c.*724+5G>C
ENST00000671940.1:c.1170+5G>C
ENST00000673490.1:n.3643+5G>C
ENST00000674923.1:c.1170+5G>C
ENST00000303395.8:c.1170+5G>C
ENST00000375405.7:c.1170+5G>C
ENST00000409050.1:c.1170+5G>C
ENST00000423058.6:c.1170+5G>C
NM_001165963.1:c.1170+5G>C
NM_001165964.1:c.1170+5G>C
NM_001202435.1:c.1170+5G>C
NM_006920.4:c.1170+5G>C
NM_001165963.2:c.1170+5G>C
NM_001165964.2:c.1170+5G>C
NM_001202435.2:c.1170+5G>C
NM_001353948.1:c.1170+5G>C
NM_001353949.1:c.1170+5G>C
NM_001353950.1:c.1170+5G>C
NM_001353951.1:c.1170+5G>C
NM_001353952.1:c.1170+5G>C
NM_001353954.1:c.1170+5G>C
NM_001353955.1:c.1170+5G>C
NM_001353957.1:c.1170+5G>C
NM_001353958.1:c.1170+5G>C
NM_001353960.1:c.1170+5G>C
NM_001353961.1:c.-1256+5G>C
NM_006920.5:c.1170+5G>C
NR_148667.1:n.1575+5G>C
NM_001165963.3:c.1170+5G>C
NM_001165964.3:c.1170+5G>C
NM_001202435.3:c.1170+5G>C
NM_001353948.2:c.1170+5G>C
NM_001353949.2:c.1170+5G>C
NM_001353950.2:c.1170+5G>C
NM_001353951.2:c.1170+5G>C
NM_001353952.2:c.1170+5G>C
NM_001353954.2:c.1170+5G>C
NM_001353955.2:c.1170+5G>C
NM_001353957.2:c.1170+5G>C
NM_001353958.2:c.1170+5G>C
NM_001353960.2:c.1170+5G>C
NM_001353961.2:c.-1256+5G>C
NM_006920.6:c.1170+5G>C
NR_148667.2:n.1556+5G>C
More

Uncertain Significance

Met criteria codes 3
PM2_Supporting PS1_Moderate PP3_Moderate
Not Met criteria codes 1
PS4

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 SCN2A Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Epilepsy Sodium Channel VCEP
The c.1170+5G>C (NM_001165963.4) variant in SCN1A is an intronic variant predicted to cause substitution of Guanine by Cytosine at nucleotide 1170+5. The variant has been reported in at least 1 proband with a phenotype of Epilepsy NOS (LabCorp Genetics Inc). It is absent from the population database gnomAD v3.1.2 and v4.0 (PM2_Supporting). The computational splicing predictor SpliceAI gives a score of 0.88 for donor loss, predicting that the variant disrupts the donor splice site of intron 11 of SCN1A (PP3_Moderate). A different variant at the same position (c.1170+5G>A)(PMID:31069529, 31440721, ClinVar ID:646111) has been classified as Likely Pathogenic for Complex Neurodevelopmental Disorder by the ClinGen Sodium Channel Variant Curation Expert Panel (PS1_Moderate). An additional variant (c.1170+5G>T) has been reported in a patient with Epilepsy NOS (ClinVar ID:851265, LabCorp Genetics Inc). However, this variant has not yet met the criteria to be classified as pathogenic or likely pathogenic by the ClinGen Sodium Channel Variant Curation Expert Panel. In summary, this variant meets the criteria to be classified as Variant of Uncertain Significance for autosomal dominant complex neurodevelopmental disorder based on the ACMG/AMP criteria applied, as specified by the ClinGen Epilepsy Sodium Channel VCEP:PS1_Moderate, PM2_Supporting, PP3_Moderate. (version 1.0; September 24, 2024).
Met criteria codes
PM2_Supporting
Absent from gnomAD v3.1.2, v.4
PS1_Moderate
c.1170+5G>A has met criteria to be classified as Likely Pathogenic by the ClinGen Sodium Channel Variant Curation Expert Panel. PS1_moderate criteria applied as per CSPEC PS1 Variants Impacting Splicing Document.
PP3_Moderate
Splice AI score = 0.88 which is above threshold of 0.2 as per Walker et al 2023 PMID:37352859
Not Met criteria codes
PS4
Total points = 0.5, insufficient for criteria cutoff.
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.