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NM_002109.6(HARS1):c.410G>A (p.Arg137Gln) AND Usher syndrome type 3B

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 24, 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:
RCV000650143.10

Allele description [Variation Report for NM_002109.6(HARS1):c.410G>A (p.Arg137Gln)]

NM_002109.6(HARS1):c.410G>A (p.Arg137Gln)

Gene:
HARS1:histidyl-tRNA synthetase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
5q31.3
Genomic location:
Preferred name:
NM_002109.6(HARS1):c.410G>A (p.Arg137Gln)
Other names:
HARS1, ARG137GLN (rs191391414)
HGVS:
  • NC_000005.10:g.140679114C>T
  • NG_032158.1:g.17273G>A
  • NM_001258040.3:c.290G>A
  • NM_001258041.3:c.410G>A
  • NM_001258042.3:c.290G>A
  • NM_001289092.2:c.301-1099G>A
  • NM_001289093.2:c.181-1099G>A
  • NM_001289094.2:c.323G>A
  • NM_002109.6:c.410G>AMANE SELECT
  • NP_001244969.1:p.Arg97Gln
  • NP_001244970.1:p.Arg137Gln
  • NP_001244971.1:p.Arg97Gln
  • NP_001276023.1:p.Arg108Gln
  • NP_002100.2:p.Arg137Gln
  • LRG_1374t1:c.410G>A
  • LRG_1374:g.17273G>A
  • LRG_1374p1:p.Arg137Gln
  • NC_000005.9:g.140058699C>T
  • NM_001258041.1:c.410G>A
  • NM_002109.3:c.410G>A
  • NM_002109.5:c.410G>A
  • P12081:p.Arg137Gln
Protein change:
R108Q; ARG137GLN
Links:
UniProtKB: P12081#VAR_069022; OMIM: 142810.0002; dbSNP: rs191391414
NCBI 1000 Genomes Browser:
rs191391414
Molecular consequence:
  • NM_001289092.2:c.301-1099G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001289093.2:c.181-1099G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001258040.3:c.290G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258041.3:c.410G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258042.3:c.290G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001289094.2:c.323G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002109.6:c.410G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Usher syndrome type 3B
Synonyms:
USHER SYNDROME, TYPE IIIB
Identifiers:
MONDO: MONDO:0013788; MedGen: C3281066; OMIM: 614504

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000771980Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 24, 2024) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies.

Tiwari A, Bahr A, Bähr L, Fleischhauer J, Zinkernagel MS, Winkler N, Barthelmes D, Berger L, Gerth-Kahlert C, Neidhardt J, Berger W.

Sci Rep. 2016 Jun 29;6:28755. doi: 10.1038/srep28755.

PubMed [citation]
PMID:
27353947
PMCID:
PMC4926080

Genomic sequencing identifies secondary findings in a cohort of parent study participants.

Thompson ML, Finnila CR, Bowling KM, Brothers KB, Neu MB, Amaral MD, Hiatt SM, East KM, Gray DE, Lawlor JMJ, Kelley WV, Lose EJ, Rich CA, Simmons S, Levy SE, Myers RM, Barsh GS, Bebin EM, Cooper GM.

Genet Med. 2018 Dec;20(12):1635-1643. doi: 10.1038/gim.2018.53. Epub 2018 Apr 12.

PubMed [citation]
PMID:
29790872
PMCID:
PMC6185813
See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000771980.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 137 of the HARS protein (p.Arg137Gln). This variant is present in population databases (rs191391414, gnomAD 0.02%). This missense change has been observed in individual(s) with HARS-related conditions (PMID: 22930593, 27353947, 29790872, 36964972). This variant is also known as c.290G>A (p.Arg97Gln). ClinVar contains an entry for this variant (Variation ID: 40062). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt HARS protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects HARS function (PMID: 22930593, 32543048). 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: May 16, 2025