NM_020117.11(LARS1):c.3289A>G (p.Ile1097Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 2, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001566128.6

Allele description [Variation Report for NM_020117.11(LARS1):c.3289A>G (p.Ile1097Val)]

NM_020117.11(LARS1):c.3289A>G (p.Ile1097Val)

Gene:

LARS1:leucyl-tRNA synthetase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q32

Genomic location:

Preferred name:

NM_020117.11(LARS1):c.3289A>G (p.Ile1097Val)

HGVS:

NC_000005.10:g.146120407T>C
NG_042294.1:g.67325A>G
NM_001317964.2:c.3151A>G
NM_001317965.2:c.3127A>G
NM_016460.4:c.3208A>G
NM_020117.11:c.3289A>GMANE SELECT
NP_001304893.1:p.Ile1051Val
NP_001304894.1:p.Ile1043Val
NP_057544.2:p.Ile1070Val
NP_064502.9:p.Ile1097Val
NC_000005.9:g.145499970T>C
NM_020117.9:c.3289A>G

Protein change:

I1043V

Links:

dbSNP: rs745902477

NCBI 1000 Genomes Browser:

rs745902477

Molecular consequence:

NM_001317964.2:c.3151A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001317965.2:c.3127A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_016460.4:c.3208A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_020117.11:c.3289A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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PREDICTED: Cricetulus griseus speedy protein E4A (LOC100767340), mRNA
PREDICTED: Cricetulus griseus speedy protein E4A (LOC100767340), mRNA
gi|1868037030|ref|XM_027440944.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001789603	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jun 21, 2021)	germline	clinical testing	Citation Link,
SCV004528998	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 2, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001789603

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jun 21, 2021)

germline

clinical testing

Citation Link,

SCV004528998

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 2, 2024)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 GeneDx, SCV001789603.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27535533)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004528998.1

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

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1097 of the LARS protein (p.Ile1097Val). This variant is present in population databases (rs745902477, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with LARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1200949). 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.

#	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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