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NM_004990.4(MARS1):c.746C>T (p.Pro249Leu) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 4, 2024
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:
RCV001065886.5

Allele description

NM_004990.4(MARS1):c.746C>T (p.Pro249Leu)

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.746C>T (p.Pro249Leu)
HGVS:
  • NC_000012.12:g.57490620C>T
  • NG_023205.2:g.3195G>A
  • NG_034077.1:g.7668C>T
  • NM_004990.4:c.746C>TMANE SELECT
  • NP_004981.2:p.Pro249Leu
  • NC_000012.11:g.57884403C>T
  • NM_004990.3:c.746C>T
Protein change:
P249L
Links:
dbSNP: rs146146070
NCBI 1000 Genomes Browser:
rs146146070
Molecular consequence:
  • NM_004990.4:c.746C>T - 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
SCV001230874Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jan 4, 2024) 		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 Invitae, SCV001230874.5

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

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 249 of the MARS protein (p.Pro249Leu). This variant is present in population databases (rs146146070, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with MARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 549700). 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. 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: Jun 17, 2024