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NM_004990.4(MARS1):c.1906A>G (p.Thr636Ala) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 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:
RCV003796359.3

Allele description [Variation Report for NM_004990.4(MARS1):c.1906A>G (p.Thr636Ala)]

NM_004990.4(MARS1):c.1906A>G (p.Thr636Ala)

Gene:
MARS1:methionyl-tRNA synthetase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q13.3
Genomic location:
Preferred name:
NM_004990.4(MARS1):c.1906A>G (p.Thr636Ala)
HGVS:
  • NC_000012.12:g.57512903A>G
  • NG_034077.1:g.29951A>G
  • NM_004990.4:c.1906A>GMANE SELECT
  • NP_004981.2:p.Thr636Ala
  • NC_000012.11:g.57906686A>G
Protein change:
T636A
Molecular consequence:
  • NM_004990.4:c.1906A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency
Synonyms:
PULMONARY ALVEOLAR PROTEINOSIS, REUNION ISLAND; Interstitial lung and liver disease
Identifiers:
MONDO: MONDO:0014206; MedGen: C4225400; OMIM: 615486
Name:
Charcot-Marie-Tooth disease axonal type 2U
Synonyms:
CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2U; CHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2U
Identifiers:
MONDO: MONDO:0014566; MedGen: C4084821; Orphanet: 397735; OMIM: 616280

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004582709Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jun 7, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV004582709.1

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

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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with MARS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 636 of the MARS protein (p.Thr636Ala).

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

Last Updated: Sep 29, 2024