ClinVar Genomic variation as it relates to human health
NM_001370259.2(MEN1):c.1673T>C (p.Met558Thr)
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.
Likely pathogenic(1); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001370259.2(MEN1):c.1673T>C (p.Met558Thr)
Variation ID: 2808810 Accession: VCV002808810.2
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.1 11: 64804494 (GRCh38) [ NCBI UCSC ] 11: 64571966 (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 Feb 20, 2024 Aug 11, 2024 May 4, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001370259.2:c.1673T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001357188.2:p.Met558Thr missense NM_000244.4:c.1688T>C NP_000235.3:p.Met563Thr missense NM_001370251.2:c.1799T>C NP_001357180.2:p.Met600Thr missense NM_001370260.2:c.1673T>C NP_001357189.2:p.Met558Thr missense NM_001370261.2:c.1673T>C NP_001357190.2:p.Met558Thr missense NM_001370262.2:c.1568T>C NP_001357191.2:p.Met523Thr missense NM_001370263.2:c.1568T>C NP_001357192.2:p.Met523Thr missense NM_001407142.1:c.1799T>C NP_001394071.1:p.Met600Thr missense NM_001407143.1:c.1799T>C NP_001394072.1:p.Met600Thr missense NM_001407144.1:c.1799T>C NP_001394073.1:p.Met600Thr missense NM_001407145.1:c.1688T>C NP_001394074.1:p.Met563Thr missense NM_001407146.1:c.1673T>C NP_001394075.1:p.Met558Thr missense NM_001407147.1:c.1673T>C NP_001394076.1:p.Met558Thr missense NM_001407148.1:c.1568T>C NP_001394077.1:p.Met523Thr missense NM_001407149.1:c.1568T>C NP_001394078.1:p.Met523Thr missense NM_001407150.1:c.1814T>C NP_001394079.1:p.Met605Thr missense NM_001407151.1:c.1694T>C NP_001394080.1:p.Met565Thr missense NM_001407152.1:c.1508T>C NP_001394081.1:p.Met503Thr missense NM_130799.3:c.1673T>C NP_570711.2:p.Met558Thr missense NM_130800.3:c.1688T>C NP_570712.2:p.Met563Thr missense NM_130801.3:c.1688T>C NP_570713.2:p.Met563Thr missense NM_130802.3:c.1688T>C NP_570714.2:p.Met563Thr missense NM_130803.3:c.1688T>C NP_570715.2:p.Met563Thr missense NM_130804.3:c.1688T>C NP_570716.2:p.Met563Thr missense NR_176284.1:n.1871T>C non-coding transcript variant NR_176285.1:n.1883T>C non-coding transcript variant NR_176286.1:n.1886T>C non-coding transcript variant NR_176287.1:n.2144T>C non-coding transcript variant NC_000011.10:g.64804494A>G NC_000011.9:g.64571966A>G NG_008929.1:g.11801T>C NG_033040.1:g.3748T>C NG_033040.2:g.3720T>C LRG_509:g.11801T>C LRG_509t1:c.1688T>C LRG_509p1:p.Met563Thr LRG_509t2:c.1673T>C LRG_509p2:p.Met558Thr - Protein change
- M523T, M563T, M605T, M503T, M558T, M565T, M600T
- Other names
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- Canonical SPDI
- NC_000011.10:64804493:A: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
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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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MEN1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2575 | 2596 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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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Oct 5, 2023 | RCV003631631.1 | |
Uncertain significance (1) |
criteria provided, single submitter
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May 4, 2024 | RCV004636796.1 |
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
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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
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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
(Oct 05, 2023)
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criteria provided, single submitter
Method: clinical testing
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Multiple endocrine neoplasia, type 1
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV004405623.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 558 of the MEN1 protein (p.Met558Thr). … (more)
This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 558 of the MEN1 protein (p.Met558Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of multiple endocrine neoplasia type 1 (Invitae). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MEN1 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
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Uncertain significance
(May 04, 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: SCV005131152.1
First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024 |
Comment:
The p.M558T variant (also known as c.1673T>C), located in coding exon 9 of the MEN1 gene, results from a T to C substitution at nucleotide … (more)
The p.M558T variant (also known as c.1673T>C), located in coding exon 9 of the MEN1 gene, results from a T to C substitution at nucleotide position 1673. The methionine at codon 558 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant 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 Aug 11, 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.