ClinVar Genomic variation as it relates to human health
NM_000251.3(MSH2):c.1433T>G (p.Leu478Arg)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000251.3(MSH2):c.1433T>G (p.Leu478Arg)
Variation ID: 1772564 Accession: VCV001772564.3
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p21 2: 47463077 (GRCh38) [ NCBI UCSC ] 2: 47690216 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Nov 29, 2022 May 1, 2024 Feb 13, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000251.3:c.1433T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000242.1:p.Leu478Arg missense NM_001258281.1:c.1235T>G NP_001245210.1:p.Leu412Arg missense NM_001406631.1:c.1433T>G NP_001393560.1:p.Leu478Arg missense NM_001406632.1:c.1433T>G NP_001393561.1:p.Leu478Arg missense NM_001406633.1:c.1433T>G NP_001393562.1:p.Leu478Arg missense NM_001406634.1:c.1433T>G NP_001393563.1:p.Leu478Arg missense NM_001406635.1:c.1433T>G NP_001393564.1:p.Leu478Arg missense NM_001406636.1:c.1400T>G NP_001393565.1:p.Leu467Arg missense NM_001406637.1:c.1433T>G NP_001393566.1:p.Leu478Arg missense NM_001406638.1:c.1472T>G NP_001393567.1:p.Leu491Arg missense NM_001406639.1:c.1433T>G NP_001393568.1:p.Leu478Arg missense NM_001406640.1:c.1433T>G NP_001393569.1:p.Leu478Arg missense NM_001406641.1:c.1433T>G NP_001393570.1:p.Leu478Arg missense NM_001406642.1:c.1433T>G NP_001393571.1:p.Leu478Arg missense NM_001406643.1:c.1433T>G NP_001393572.1:p.Leu478Arg missense NM_001406644.1:c.1433T>G NP_001393573.1:p.Leu478Arg missense NM_001406645.1:c.1433T>G NP_001393574.1:p.Leu478Arg missense NM_001406646.1:c.1433T>G NP_001393575.1:p.Leu478Arg missense NM_001406647.1:c.1283T>G NP_001393576.1:p.Leu428Arg missense NM_001406648.1:c.1433T>G NP_001393577.1:p.Leu478Arg missense NM_001406649.1:c.1283T>G NP_001393578.1:p.Leu428Arg missense NM_001406650.1:c.1283T>G NP_001393579.1:p.Leu428Arg missense NM_001406651.1:c.1283T>G NP_001393580.1:p.Leu428Arg missense NM_001406652.1:c.1283T>G NP_001393581.1:p.Leu428Arg missense NM_001406653.1:c.1373T>G NP_001393582.1:p.Leu458Arg missense NM_001406654.1:c.1013T>G NP_001393583.1:p.Leu338Arg missense NM_001406655.1:c.1433T>G NP_001393584.1:p.Leu478Arg missense NM_001406656.1:c.536T>G NP_001393585.1:p.Leu179Arg missense NM_001406657.1:c.1433T>G NP_001393586.1:p.Leu478Arg missense NM_001406658.1:c.77T>G NP_001393587.1:p.Leu26Arg missense NM_001406659.1:c.77T>G NP_001393588.1:p.Leu26Arg missense NM_001406660.1:c.77T>G NP_001393589.1:p.Leu26Arg missense NM_001406661.1:c.77T>G NP_001393590.1:p.Leu26Arg missense NM_001406662.1:c.77T>G NP_001393591.1:p.Leu26Arg missense NM_001406669.1:c.77T>G NP_001393598.1:p.Leu26Arg missense NM_001406674.1:c.1433T>G NP_001393603.1:p.Leu478Arg missense NR_176230.1:n.1469T>G NR_176231.1:n.1469T>G NR_176232.1:n.1469T>G NR_176233.1:n.1311T>G NR_176234.1:n.1469T>G NR_176235.1:n.1469T>G NR_176236.1:n.1469T>G NR_176237.1:n.1469T>G NR_176238.1:n.1469T>G NR_176239.1:n.1469T>G NR_176240.1:n.1469T>G NR_176241.1:n.1469T>G NR_176242.1:n.1469T>G NR_176243.1:n.1319T>G NR_176244.1:n.1469T>G NR_176245.1:n.1469T>G NR_176246.1:n.1469T>G NR_176247.1:n.1469T>G NR_176248.1:n.1469T>G NR_176249.1:n.1699T>G NR_176250.1:n.1209T>G NC_000002.12:g.47463077T>G NC_000002.11:g.47690216T>G NG_007110.2:g.64954T>G LRG_218:g.64954T>G LRG_218t1:c.1433T>G LRG_218p1:p.Leu478Arg - Protein change
- L412R, L458R, L467R, L338R, L26R, L491R, L179R, L428R, L478R
- Other names
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- Canonical SPDI
- NC_000002.12:47463076:T:G
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MSH2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
7394 | 7556 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Likely pathogenic (1) |
criteria provided, single submitter
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Feb 13, 2024 | RCV002392126.2 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Aug 2, 2023 | RCV003454250.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely pathogenic
(Aug 02, 2023)
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criteria provided, single submitter
Method: clinical testing
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Lynch syndrome 1
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004186656.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
Comment:
This variant is considered likely pathogenic. This variant is expected to disrupt protein structure [Myriad internal data]. Functional studies indicate this variant impacts protein function … (more)
This variant is considered likely pathogenic. This variant is expected to disrupt protein structure [Myriad internal data]. Functional studies indicate this variant impacts protein function [PMID: 33357406]. (less)
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Likely pathogenic
(Feb 13, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV002696214.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.L478R variant (also known as c.1433T>G), located in coding exon 9 of the MSH2 gene, results from a T to G substitution at nucleotide … (more)
The p.L478R variant (also known as c.1433T>G), located in coding exon 9 of the MSH2 gene, results from a T to G substitution at nucleotide position 1433. The leucine at codon 478 is replaced by arginine, an amino acid with dissimilar properties. In a massively parallel cell-based functional assay testing susceptibility to a DNA damaging agent, 6-thioguanine (6-TG), this variant was reported to be functionally deleterious (Jia X et al. Am J Hum Genet, 2021 01;108:163-175). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk. | Jia X | American journal of human genetics | 2021 | PMID: 33357406 |
Text-mined citations for this variant ...
HelpRecord last updated Jun 10, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.