NM_001165963.4(SCN1A):c.5726C>T (p.Thr1909Ile) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: May 1, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000494436.3

Allele description [Variation Report for NM_001165963.4(SCN1A):c.5726C>T (p.Thr1909Ile)]

NM_001165963.4(SCN1A):c.5726C>T (p.Thr1909Ile)

Genes:
SCN1A:sodium voltage-gated channel alpha subunit 1 [Gene - OMIM - HGNC]
LOC102724058:uncharacterized LOC102724058 [Gene]
Variant type:
single nucleotide variant
Cytogenetic location:
2q24.3
Genomic location:
Preferred name:
NM_001165963.4(SCN1A):c.5726C>T (p.Thr1909Ile)
HGVS:
  • NC_000002.12:g.165991549G>A
  • NG_011906.1:g.87091C>T
  • NM_001165963.4:c.5726C>TMANE SELECT
  • NM_001165963.4:c.5726C>T
  • NM_001165964.3:c.5642C>T
  • NM_001202435.3:c.5726C>T
  • NM_001353948.2:c.5726C>T
  • NM_001353949.2:c.5693C>T
  • NM_001353950.2:c.5693C>T
  • NM_001353951.2:c.5693C>T
  • NM_001353952.2:c.5693C>T
  • NM_001353954.2:c.5690C>T
  • NM_001353955.2:c.5690C>T
  • NM_001353957.2:c.5642C>T
  • NM_001353958.2:c.5642C>T
  • NM_001353960.2:c.5639C>T
  • NM_001353961.2:c.3284C>T
  • NM_006920.6:c.5693C>T
  • NP_001159435.1:p.Thr1909Ile
  • NP_001159436.1:p.Thr1881Ile
  • NP_001189364.1:p.Thr1909Ile
  • NP_001340877.1:p.Thr1909Ile
  • NP_001340878.1:p.Thr1898Ile
  • NP_001340879.1:p.Thr1898Ile
  • NP_001340880.1:p.Thr1898Ile
  • NP_001340881.1:p.Thr1898Ile
  • NP_001340883.1:p.Thr1897Ile
  • NP_001340884.1:p.Thr1897Ile
  • NP_001340886.1:p.Thr1881Ile
  • NP_001340887.1:p.Thr1881Ile
  • NP_001340889.1:p.Thr1880Ile
  • NP_001340890.1:p.Thr1095Ile
  • NP_008851.3:p.Thr1898Ile
  • LRG_8t1:c.5693C>T
  • LRG_8:g.87091C>T
  • NC_000002.11:g.166848059G>A
  • NM_001165963.1:c.5726C>T
  • NM_006920.4:c.5693C>T
  • NR_148667.2:n.6143C>T
Protein change:
T1095I
Links:
UniProtKB/Swiss-Prot: VAR_029729; dbSNP: rs121918793
NCBI 1000 Genomes Browser:
rs121918793
Molecular consequence:
  • NM_001165963.4:c.5726C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001165964.3:c.5642C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001202435.3:c.5726C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353948.2:c.5726C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353949.2:c.5693C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353950.2:c.5693C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353951.2:c.5693C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353952.2:c.5693C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353954.2:c.5690C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353955.2:c.5690C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353957.2:c.5642C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353958.2:c.5642C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353960.2:c.5639C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353961.2:c.3284C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006920.6:c.5693C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_148667.2:n.6143C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000581895GeneDxcriteria provided, single submitter
Likely pathogenic
(May 1, 2017)
germlineclinical testing

Citation Link,

SCV001245858CeGaT Praxis fuer Humangenetik Tuebingencriteria provided, single submitter
Pathogenic
(May 1, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000581895.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

A variant that is likely pathogenic has been identified in the SCN1A gene. The T1909I variant has been previously reported as T1899I (using alternative nomenclature) in an individual with severe myoclonic epilepsy of infancy; parental testing was not reported (Ohmori et al., 2002). Functional studies have demonstrated that T1909I results in a abnormal channel function (Ohmori et al., 2006). The T1909I variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The T1909I variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution alters a conserved position predicted to be within the C-terminal cytoplasmic domain. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From CeGaT Praxis fuer Humangenetik Tuebingen, SCV001245858.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Nov 27, 2021

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