NM_001330260.2(SCN8A):c.5620G>C (p.Val1874Leu) AND Cognitive impairment with or without cerebellar ataxia

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Nov 24, 2022
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002226923.4

Allele description [Variation Report for NM_001330260.2(SCN8A):c.5620G>C (p.Val1874Leu)]

NM_001330260.2(SCN8A):c.5620G>C (p.Val1874Leu)

Gene:

SCN8A:sodium voltage-gated channel alpha subunit 8 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q13.13

Genomic location:

Preferred name:

NM_001330260.2(SCN8A):c.5620G>C (p.Val1874Leu)

HGVS:

NC_000012.12:g.51807106G>C
NG_021180.3:g.222149G>C
NM_001177984.3:c.5497G>C
NM_001330260.2:c.5620G>CMANE SELECT
NM_001369788.1:c.5497G>C
NM_014191.4:c.5620G>C
NP_001171455.1:p.Val1833Leu
NP_001317189.1:p.Val1874Leu
NP_001356717.1:p.Val1833Leu
NP_055006.1:p.Val1874Leu
LRG_1389t1:c.5620G>C
LRG_1389t2:c.5620G>C
LRG_1389:g.222149G>C
LRG_1389p1:p.Val1874Leu
LRG_1389p2:p.Val1874Leu
NC_000012.11:g.52200890G>C
NM_014191.3:c.5620G>C

Protein change:

V1833L

Links:

dbSNP: rs781602116

NCBI 1000 Genomes Browser:

rs781602116

Molecular consequence:

NM_001177984.3:c.5497G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001330260.2:c.5620G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001369788.1:c.5497G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_014191.4:c.5620G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cognitive impairment with or without cerebellar ataxia (CIAT)
Identifiers:: MONDO: MONDO:0013680; MedGen: C3280415; OMIM: 614306

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002505824	Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 1, 2021)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002765067	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 24, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002505824

Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Aug 1, 2021)

de novo

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002765067

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 24, 2022)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	de novo	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet, SCV002505824.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Human Genetics, University of Leipzig Medical Center, SCV002765067.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

_x000D_ Criteria applied: PM1, PS4_SUP, PM2_SUP, PP3

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 4, 2024

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