ClinVar Genomic variation as it relates to human health
NM_000535.7(PMS2):c.1321G>A (p.Glu441Lys)
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_000535.7(PMS2):c.1321G>A (p.Glu441Lys)
Variation ID: 2451633 Accession: VCV002451633.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 7p22.1 7: 5987444 (GRCh38) [ NCBI UCSC ] 7: 6027075 (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 Apr 15, 2023 May 1, 2024 Mar 12, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000535.7:c.1321G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000526.2:p.Glu441Lys missense NM_001018040.1:c.916G>A NP_001018050.1:p.Glu306Lys missense NM_001322003.2:c.916G>A NP_001308932.1:p.Glu306Lys missense NM_001322004.2:c.916G>A NP_001308933.1:p.Glu306Lys missense NM_001322005.2:c.916G>A NP_001308934.1:p.Glu306Lys missense NM_001322006.2:c.1165G>A NP_001308935.1:p.Glu389Lys missense NM_001322007.2:c.1003G>A NP_001308936.1:p.Glu335Lys missense NM_001322008.2:c.1003G>A NP_001308937.1:p.Glu335Lys missense NM_001322009.2:c.916G>A NP_001308938.1:p.Glu306Lys missense NM_001322010.2:c.760G>A NP_001308939.1:p.Glu254Lys missense NM_001322011.2:c.388G>A NP_001308940.1:p.Glu130Lys missense NM_001322012.2:c.388G>A NP_001308941.1:p.Glu130Lys missense NM_001322013.2:c.748G>A NP_001308942.1:p.Glu250Lys missense NM_001322014.2:c.1321G>A NP_001308943.1:p.Glu441Lys missense NM_001322015.2:c.1012G>A NP_001308944.1:p.Glu338Lys missense NM_001406866.1:c.1507G>A NP_001393795.1:p.Glu503Lys missense NM_001406868.1:c.1345G>A NP_001393797.1:p.Glu449Lys missense NM_001406869.1:c.1213G>A NP_001393798.1:p.Glu405Lys missense NM_001406870.1:c.1165G>A NP_001393799.1:p.Glu389Lys missense NM_001406871.1:c.1321G>A NP_001393800.1:p.Glu441Lys missense NM_001406872.1:c.1321G>A NP_001393801.1:p.Glu441Lys missense NM_001406873.1:c.1123G>A NP_001393802.1:p.Glu375Lys missense NM_001406874.1:c.1153G>A NP_001393803.1:p.Glu385Lys missense NM_001406875.1:c.1012G>A NP_001393804.1:p.Glu338Lys missense NM_001406876.1:c.1003G>A NP_001393805.1:p.Glu335Lys missense NM_001406877.1:c.1012G>A NP_001393806.1:p.Glu338Lys missense NM_001406878.1:c.1012G>A NP_001393807.1:p.Glu338Lys missense NM_001406879.1:c.1012G>A NP_001393808.1:p.Glu338Lys missense NM_001406880.1:c.1012G>A NP_001393809.1:p.Glu338Lys missense NM_001406881.1:c.1012G>A NP_001393810.1:p.Glu338Lys missense NM_001406882.1:c.1012G>A NP_001393811.1:p.Glu338Lys missense NM_001406883.1:c.1003G>A NP_001393812.1:p.Glu335Lys missense NM_001406884.1:c.997G>A NP_001393813.1:p.Glu333Lys missense NM_001406885.1:c.985G>A NP_001393814.1:p.Glu329Lys missense NM_001406886.1:c.955G>A NP_001393815.1:p.Glu319Lys missense NM_001406887.1:c.916G>A NP_001393816.1:p.Glu306Lys missense NM_001406888.1:c.916G>A NP_001393817.1:p.Glu306Lys missense NM_001406889.1:c.916G>A NP_001393818.1:p.Glu306Lys missense NM_001406890.1:c.916G>A NP_001393819.1:p.Glu306Lys missense NM_001406891.1:c.916G>A NP_001393820.1:p.Glu306Lys missense NM_001406892.1:c.916G>A NP_001393821.1:p.Glu306Lys missense NM_001406893.1:c.916G>A NP_001393822.1:p.Glu306Lys missense NM_001406894.1:c.916G>A NP_001393823.1:p.Glu306Lys missense NM_001406895.1:c.916G>A NP_001393824.1:p.Glu306Lys missense NM_001406896.1:c.916G>A NP_001393825.1:p.Glu306Lys missense NM_001406897.1:c.916G>A NP_001393826.1:p.Glu306Lys missense NM_001406898.1:c.916G>A NP_001393827.1:p.Glu306Lys missense NM_001406899.1:c.916G>A NP_001393828.1:p.Glu306Lys missense NM_001406900.1:c.856G>A NP_001393829.1:p.Glu286Lys missense NM_001406901.1:c.847G>A NP_001393830.1:p.Glu283Lys missense NM_001406902.1:c.847G>A NP_001393831.1:p.Glu283Lys missense NM_001406903.1:c.1003G>A NP_001393832.1:p.Glu335Lys missense NM_001406904.1:c.808G>A NP_001393833.1:p.Glu270Lys missense NM_001406905.1:c.808G>A NP_001393834.1:p.Glu270Lys missense NM_001406906.1:c.760G>A NP_001393835.1:p.Glu254Lys missense NM_001406907.1:c.760G>A NP_001393836.1:p.Glu254Lys missense NM_001406908.1:c.916G>A NP_001393837.1:p.Glu306Lys missense NM_001406909.1:c.748G>A NP_001393838.1:p.Glu250Lys missense NM_001406910.1:c.916G>A NP_001393839.1:p.Glu306Lys missense NM_001406911.1:c.550G>A NP_001393840.1:p.Glu184Lys missense NM_001406912.1:c.804-4453G>A intron variant NR_003085.2:n.1403G>A NR_136154.1:n.1408G>A non-coding transcript variant NC_000007.14:g.5987444C>T NC_000007.13:g.6027075C>T NG_008466.1:g.26663G>A LRG_161:g.26663G>A LRG_161t1:c.1321G>A LRG_161p1:p.Glu441Lys - Protein change
- E306K, E319K, E449K, E250K, E283K, E329K, E333K, E503K, E254K, E286K, E335K, E375K, E441K, E130K, E184K, E270K, E338K, E385K, E389K, E405K
- Other names
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- Canonical SPDI
- NC_000007.14:5987443:C:T
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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
Help
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
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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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PMS2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
5240 | 5342 |
Conditions - Germline
Condition
Help
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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Uncertain significance (1) |
criteria provided, single submitter
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Mar 12, 2023 | RCV003187329.2 |
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
Help
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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Uncertain significance
(Mar 12, 2023)
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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: SCV003853946.2
First in ClinVar: Apr 15, 2023 Last updated: May 01, 2024 |
Comment:
The p.E441K variant (also known as c.1321G>A), located in coding exon 11 of the PMS2 gene, results from a G to A substitution at nucleotide … (more)
The p.E441K variant (also known as c.1321G>A), located in coding exon 11 of the PMS2 gene, results from a G to A substitution at nucleotide position 1321. The glutamic acid at codon 441 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated May 01, 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.