ClinVar Genomic variation as it relates to human health
NM_198252.3(GSN):c.1585G>A (p.Glu529Lys)
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_198252.3(GSN):c.1585G>A (p.Glu529Lys)
Variation ID: 930592 Accession: VCV000930592.6
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 9q33.2 9: 121326680 (GRCh38) [ NCBI UCSC ] 9: 124088958 (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 Jul 4, 2020 May 26, 2024 Sep 16, 2019 - HGVS
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Nucleotide Protein Molecular
consequenceNM_198252.3:c.1585G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_937895.1:p.Glu529Lys missense NM_000177.5:c.1738G>A NP_000168.1:p.Glu580Lys missense NM_001127662.2:c.1585G>A NP_001121134.1:p.Glu529Lys missense NM_001127663.2:c.1693G>A NP_001121135.2:p.Glu565Lys missense NM_001127664.2:c.1585G>A NP_001121136.1:p.Glu529Lys missense NM_001127665.2:c.1585G>A NP_001121137.1:p.Glu529Lys missense NM_001127666.2:c.1618G>A NP_001121138.1:p.Glu540Lys missense NM_001127667.2:c.1618G>A NP_001121139.1:p.Glu540Lys missense NM_001258029.2:c.1636G>A NP_001244958.1:p.Glu546Lys missense NM_001258030.2:c.1609G>A NP_001244959.1:p.Glu537Lys missense NM_001353053.1:c.1585G>A NP_001339982.1:p.Glu529Lys missense NM_001353054.1:c.1585G>A NP_001339983.1:p.Glu529Lys missense NM_001353055.2:c.1585G>A NP_001339984.1:p.Glu529Lys missense NM_001353056.2:c.1585G>A NP_001339985.1:p.Glu529Lys missense NM_001353057.2:c.1585G>A NP_001339986.1:p.Glu529Lys missense NM_001353058.2:c.1585G>A NP_001339987.1:p.Glu529Lys missense NM_001353059.2:c.1585G>A NP_001339988.1:p.Glu529Lys missense NM_001353060.2:c.1585G>A NP_001339989.1:p.Glu529Lys missense NM_001353061.2:c.1585G>A NP_001339990.1:p.Glu529Lys missense NM_001353062.1:c.1585G>A NP_001339991.1:p.Glu529Lys missense NM_001353063.2:c.1618G>A NP_001339992.1:p.Glu540Lys missense NM_001353064.2:c.1618G>A NP_001339993.1:p.Glu540Lys missense NM_001353065.2:c.1618G>A NP_001339994.1:p.Glu540Lys missense NM_001353066.2:c.1618G>A NP_001339995.1:p.Glu540Lys missense NM_001353067.2:c.1618G>A NP_001339996.1:p.Glu540Lys missense NM_001353068.2:c.1618G>A NP_001339997.1:p.Glu540Lys missense NM_001353069.2:c.1618G>A NP_001339998.1:p.Glu540Lys missense NM_001353070.2:c.1618G>A NP_001339999.1:p.Glu540Lys missense NM_001353071.2:c.1618G>A NP_001340000.1:p.Glu540Lys missense NM_001353072.2:c.1618G>A NP_001340001.1:p.Glu540Lys missense NM_001353073.2:c.1618G>A NP_001340002.1:p.Glu540Lys missense NM_001353074.2:c.1618G>A NP_001340003.1:p.Glu540Lys missense NM_001353075.1:c.1618G>A NP_001340004.1:p.Glu540Lys missense NM_001353076.2:c.1657G>A NP_001340005.1:p.Glu553Lys missense NM_001353077.1:c.1618G>A NP_001340006.1:p.Glu540Lys missense NM_001353078.2:c.931G>A NP_001340007.1:p.Glu311Lys missense NC_000009.12:g.121326680G>A NC_000009.11:g.124088958G>A NG_012872.2:g.130599G>A - Protein change
- E529K, E540K, E553K, E580K, E311K, E537K, E546K, E565K
- Other names
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- Canonical SPDI
- NC_000009.12:121326679:G:A
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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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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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GSN | - | - |
GRCh38 GRCh37 |
714 | 749 |
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
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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 (2) |
criteria provided, single submitter
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Sep 16, 2019 | RCV001196370.3 |
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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Uncertain significance
(Sep 16, 2019)
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criteria provided, single submitter
Method: clinical testing
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Finnish type amyloidosis
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001366977.2
First in ClinVar: Jul 04, 2020 Last updated: Jul 04, 2020 |
Comment:
This variant was classified as: Uncertain significance. The available evidence favors the pathogenic nature of this variant, however the currently available data is insufficient to … (more)
This variant was classified as: Uncertain significance. The available evidence favors the pathogenic nature of this variant, however the currently available data is insufficient to conclusively support its pathogenic nature. Thus this variant is classified as Uncertain significance - favor pathogenic. The following ACMG criteria were applied in classifying this variant: PM2,PP3,BP1. (less)
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Pathogenic
(May 17, 2024)
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no assertion criteria provided
Method: literature only
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AMYLOIDOSIS, FINNISH TYPE
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV004028541.2
First in ClinVar: Aug 26, 2023 Last updated: May 26, 2024 |
Comment on evidence:
In 6 members of a family with Finnish-type amyloidosis (105120), Potrc et al. (2021) identified a heterozygous c.1738G-A transition (c.1738G-A, NM_000177.5) in the GSN gene, … (more)
In 6 members of a family with Finnish-type amyloidosis (105120), Potrc et al. (2021) identified a heterozygous c.1738G-A transition (c.1738G-A, NM_000177.5) in the GSN gene, resulting in a glu580-to-lys (E580K) substitution. The variant segregated with the disease in the family and was not present in the gnomAD database. The affected residue was located in the G5 domain, which is homologous to the second domain, which contains D187N (137350.0001), the most common pathogenic variant. (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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Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel GSN Variant p.Glu580Lys. | Potrč M | International journal of molecular sciences | 2021 | PMID: 33499149 |
Text-mined citations for rs2063220897 ...
HelpRecord last updated Jun 02, 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.