NM_018834.6(MATR3):c.196C>A (p.Gln66Lys) AND Amyotrophic lateral sclerosis type 21

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 7, 2023
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:: RCV003516303.2

Allele description [Variation Report for NM_018834.6(MATR3):c.196C>A (p.Gln66Lys)]

NM_018834.6(MATR3):c.196C>A (p.Gln66Lys)

Gene:

MATR3:matrin 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q31.2

Genomic location:

Preferred name:

NM_018834.6(MATR3):c.196C>A (p.Gln66Lys)

HGVS:

NC_000005.10:g.139307611C>A
NG_012846.1:g.38509C>A
NM_001194954.2:c.196C>A
NM_001194955.2:c.196C>A
NM_001194956.2:c.49-7064C>A
NM_001282278.2:c.-102-7064C>A
NM_001400441.1:c.196C>A
NM_001400442.1:c.196C>A
NM_001400443.1:c.196C>A
NM_001400444.1:c.196C>A
NM_001400445.1:c.196C>A
NM_001400447.1:c.196C>A
NM_001400448.1:c.196C>A
NM_001400450.1:c.196C>A
NM_001400451.1:c.196C>A
NM_001400452.1:c.196C>A
NM_001400453.1:c.196C>A
NM_001400454.1:c.196C>A
NM_001400455.1:c.196C>A
NM_001400456.1:c.196C>A
NM_001400457.1:c.196C>A
NM_001400458.1:c.196C>A
NM_001400459.1:c.52-7064C>A
NM_001400460.1:c.-102-7064C>A
NM_001400461.1:c.13-7064C>A
NM_001400462.1:c.-40-8086C>A
NM_001400463.1:c.-102-7064C>A
NM_001400464.1:c.-102-7064C>A
NM_001400465.1:c.-102-7064C>A
NM_001400466.1:c.-102-7064C>A
NM_001400467.1:c.-40-8086C>A
NM_018834.6:c.196C>AMANE SELECT
NM_199189.3:c.196C>A
NP_001181883.1:p.Gln66Lys
NP_001181884.1:p.Gln66Lys
NP_001387370.1:p.Gln66Lys
NP_001387371.1:p.Gln66Lys
NP_001387372.1:p.Gln66Lys
NP_001387373.1:p.Gln66Lys
NP_001387374.1:p.Gln66Lys
NP_001387376.1:p.Gln66Lys
NP_001387377.1:p.Gln66Lys
NP_001387379.1:p.Gln66Lys
NP_001387380.1:p.Gln66Lys
NP_001387381.1:p.Gln66Lys
NP_001387382.1:p.Gln66Lys
NP_001387383.1:p.Gln66Lys
NP_001387384.1:p.Gln66Lys
NP_001387385.1:p.Gln66Lys
NP_001387386.1:p.Gln66Lys
NP_001387387.1:p.Gln66Lys
NP_061322.2:p.Gln66Lys
NP_954659.1:p.Gln66Lys
NC_000005.9:g.138643300C>A

Protein change:

Q66K

Molecular consequence:

NM_001194956.2:c.49-7064C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001282278.2:c.-102-7064C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001400459.1:c.52-7064C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001400460.1:c.-102-7064C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001400461.1:c.13-7064C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001400462.1:c.-40-8086C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001400463.1:c.-102-7064C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001400464.1:c.-102-7064C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001400465.1:c.-102-7064C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001400466.1:c.-102-7064C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001400467.1:c.-40-8086C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001194954.2:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001194955.2:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001400441.1:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001400442.1:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001400443.1:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001400444.1:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001400445.1:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001400447.1:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001400448.1:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001400450.1:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001400451.1:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001400452.1:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001400453.1:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001400454.1:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001400455.1:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001400456.1:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001400457.1:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001400458.1:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_018834.6:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_199189.3:c.196C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Amyotrophic lateral sclerosis type 21
Synonyms:: VOCAL CORD AND PHARYNGEAL DYSFUNCTION WITH DISTAL MYOPATHY; Myopathy, distal, 2
Identifiers:: MONDO: MONDO:0011632; MedGen: C3807521; Orphanet: 600; Orphanet: 803; OMIM: 606070

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004292863	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 7, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30015619, 28029397, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004292863

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 7, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Matrin 3-dependent neurotoxicity is modified by nucleic acid binding and nucleocytoplasmic localization.

Malik AM, Miguez RA, Li X, Ho YS, Feldman EL, Barmada SJ.

Elife. 2018 Jul 17;7. doi:pii: e35977. 10.7554/eLife.35977.

PubMed [citation]

PMID:: 30015619
PMCID:: PMC6050042

Matrin 3 variants are frequent in Italian ALS patients.

Marangi G, Lattante S, Doronzio PN, Conte A, Tasca G, Monforte M, Patanella AK, Bisogni G, Meleo E, La Spada S, Zollino M, Sabatelli M.

Neurobiol Aging. 2017 Jan;49:218.e1-218.e7. doi: 10.1016/j.neurobiolaging.2016.09.023. Epub 2016 Oct 6.

PubMed [citation]

PMID:: 28029397

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004292863.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on MATR3 function (PMID: 30015619). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MATR3 protein function. This missense change has been observed in individuals with amyotrophic lateral sclerosis (PMID: 28029397; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 66 of the MATR3 protein (p.Gln66Lys).

#	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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