NM_015046.7(SETX):c.4045C>G (p.Gln1349Glu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 19, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000644816.7

Allele description [Variation Report for NM_015046.7(SETX):c.4045C>G (p.Gln1349Glu)]

NM_015046.7(SETX):c.4045C>G (p.Gln1349Glu)

Gene:

SETX:senataxin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q34.13

Genomic location:

Preferred name:

NM_015046.7(SETX):c.4045C>G (p.Gln1349Glu)

HGVS:

NC_000009.12:g.132327553G>C
NG_007946.1:g.32433C>G
NM_001351527.2:c.4045C>G
NM_001351528.2:c.4045C>G
NM_015046.7:c.4045C>GMANE SELECT
NP_001338456.1:p.Gln1349Glu
NP_001338457.1:p.Gln1349Glu
NP_055861.3:p.Gln1349Glu
LRG_268t1:c.4045C>G
LRG_268:g.32433C>G
NC_000009.11:g.135202940G>C
NM_015046.5:c.4045C>G

Protein change:

Q1349E

Links:

dbSNP: rs146407699

NCBI 1000 Genomes Browser:

rs146407699

Molecular consequence:

NM_001351527.2:c.4045C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001351528.2:c.4045C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_015046.7:c.4045C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Amyotrophic lateral sclerosis type 4 (ALS4)
Synonyms:: AMYOTROPHIC LATERAL SCLEROSIS 4, JUVENILE; NEURONOPATHY, DISTAL HEREDITARY MOTOR, WITH PYRAMIDAL FEATURES
Identifiers:: MONDO: MONDO:0011223; MedGen: C1865409; Orphanet: 357043; OMIM: 602433

Name:: Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (SCAN2)
Synonyms:: Ataxia-oculomotor apraxia 2; Ataxia-ocular apraxia-2; Ataxia with Oculomotor Apraxia
Identifiers:: MONDO: MONDO:0018996; MedGen: C1853761; Orphanet: 64753; OMIM: 606002

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000766531	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 19, 2021)	germline	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

SCV000766531

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 19, 2021)

germline

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	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000766531.4

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

Description

This sequence change replaces glutamine with glutamic acid at codon 1349 of the SETX protein (p.Gln1349Glu). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and glutamic acid. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SETX-related disease. This variant is not present in population databases (ExAC no frequency).

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

Last Updated: Sep 29, 2024

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