NM_018834.6(MATR3):c.2525G>C (p.Arg842Thr) AND Amyotrophic lateral sclerosis 21

Clinical significance:Uncertain significance (Last evaluated: Jul 20, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000808402.3

Allele description [Variation Report for NM_018834.6(MATR3):c.2525G>C (p.Arg842Thr)]

NM_018834.6(MATR3):c.2525G>C (p.Arg842Thr)

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.2525G>C (p.Arg842Thr)
HGVS:
  • NC_000005.10:g.139329376G>C
  • NG_012846.1:g.60274G>C
  • NM_001194954.2:c.2525G>C
  • NM_001194955.2:c.2525G>C
  • NM_001194956.2:c.1661G>C
  • NM_001282278.2:c.1511G>C
  • NM_018834.6:c.2525G>CMANE SELECT
  • NM_199189.3:c.2525G>C
  • NP_001181883.1:p.Arg842Thr
  • NP_001181884.1:p.Arg842Thr
  • NP_001181885.1:p.Arg554Thr
  • NP_001269207.1:p.Arg504Thr
  • NP_061322.2:p.Arg842Thr
  • NP_954659.1:p.Arg842Thr
  • NP_954659.1:p.Arg842Thr
  • NC_000005.9:g.138665065G>C
  • NM_199189.2:c.2525G>C
Protein change:
R504T
Links:
dbSNP: rs749235364
NCBI 1000 Genomes Browser:
rs749235364
Molecular consequence:
  • NM_001194954.2:c.2525G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001194955.2:c.2525G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001194956.2:c.1661G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282278.2:c.1511G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_018834.6:c.2525G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_199189.3:c.2525G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Amyotrophic lateral sclerosis 21 (ALS21)
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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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000948511Invitaecriteria provided, single submitter
Uncertain significance
(Jul 20, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation.

Kobayashi Y, Yang S, Nykamp K, Garcia J, Lincoln SE, Topper SE.

Genome Med. 2017 Feb 6;9(1):13. doi: 10.1186/s13073-017-0403-7.

PubMed [citation]
PMID:
28166811
PMCID:
PMC5295186

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000948511.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces arginine with threonine at codon 842 of the MATR3 protein (p.Arg842Thr). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and threonine. This variant is present in population databases (rs749235364, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with MATR3-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). 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.

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

Last Updated: Dec 4, 2021

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