VCV000984957.10 - ClinVar

NM_198252.3(GSN):c.1324T>C (p.Trp442Arg)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Uncertain significance
Uncertain significance (2)

2 out of 3 submissions contributed to this classification

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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_198252.3(GSN):c.1324T>C (p.Trp442Arg)

Variation ID: 984957 Accession: VCV000984957.10

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 9q33.2 9: 121321400 (GRCh38) [ NCBI UCSC ] 9: 124083678 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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 21, 2020	Jul 14, 2026	Nov 15, 2020

HGVS

Nucleotide	Protein	Molecular consequence
NM_198252.3:c.1324T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_937895.1:p.Trp442Arg	missense
NM_000177.4:c.1477T>C
NM_000177.5:c.1477T>C	NP_000168.1:p.Trp493Arg	missense
NM_001127662.2:c.1324T>C	NP_001121134.1:p.Trp442Arg	missense
NM_001127663.2:c.1432T>C	NP_001121135.2:p.Trp478Arg	missense
NM_001127664.2:c.1324T>C	NP_001121136.1:p.Trp442Arg	missense
NM_001127665.2:c.1324T>C	NP_001121137.1:p.Trp442Arg	missense
NM_001127666.2:c.1357T>C	NP_001121138.1:p.Trp453Arg	missense
NM_001127667.2:c.1357T>C	NP_001121139.1:p.Trp453Arg	missense
NM_001258029.2:c.1375T>C	NP_001244958.1:p.Trp459Arg	missense
NM_001258030.2:c.1348T>C	NP_001244959.1:p.Trp450Arg	missense
NM_001353053.1:c.1324T>C	NP_001339982.1:p.Trp442Arg	missense
NM_001353054.1:c.1324T>C	NP_001339983.1:p.Trp442Arg	missense
NM_001353055.2:c.1324T>C	NP_001339984.1:p.Trp442Arg	missense
NM_001353056.2:c.1324T>C	NP_001339985.1:p.Trp442Arg	missense
NM_001353057.2:c.1324T>C	NP_001339986.1:p.Trp442Arg	missense
NM_001353058.2:c.1324T>C	NP_001339987.1:p.Trp442Arg	missense
NM_001353059.2:c.1324T>C	NP_001339988.1:p.Trp442Arg	missense
NM_001353060.2:c.1324T>C	NP_001339989.1:p.Trp442Arg	missense
NM_001353061.2:c.1324T>C	NP_001339990.1:p.Trp442Arg	missense
NM_001353062.1:c.1324T>C	NP_001339991.1:p.Trp442Arg	missense
NM_001353063.2:c.1357T>C	NP_001339992.1:p.Trp453Arg	missense
NM_001353064.2:c.1357T>C	NP_001339993.1:p.Trp453Arg	missense
NM_001353065.2:c.1357T>C	NP_001339994.1:p.Trp453Arg	missense
NM_001353066.2:c.1357T>C	NP_001339995.1:p.Trp453Arg	missense
NM_001353067.2:c.1357T>C	NP_001339996.1:p.Trp453Arg	missense
NM_001353068.2:c.1357T>C	NP_001339997.1:p.Trp453Arg	missense
NM_001353069.2:c.1357T>C	NP_001339998.1:p.Trp453Arg	missense
NM_001353070.2:c.1357T>C	NP_001339999.1:p.Trp453Arg	missense
NM_001353071.2:c.1357T>C	NP_001340000.1:p.Trp453Arg	missense
NM_001353072.2:c.1357T>C	NP_001340001.1:p.Trp453Arg	missense
NM_001353073.2:c.1357T>C	NP_001340002.1:p.Trp453Arg	missense
NM_001353074.2:c.1357T>C	NP_001340003.1:p.Trp453Arg	missense
NM_001353075.1:c.1357T>C	NP_001340004.1:p.Trp453Arg	missense
NM_001353076.2:c.1396T>C	NP_001340005.1:p.Trp466Arg	missense
NM_001353077.1:c.1357T>C	NP_001340006.1:p.Trp453Arg	missense
NM_001353078.2:c.670T>C	NP_001340007.1:p.Trp224Arg	missense
NC_000009.12:g.121321400T>C
NC_000009.11:g.124083678T>C
NG_012872.2:g.125319T>C

... more HGVS ... less HGVS

Protein change

W224R, W442R, W450R, W453R, W459R, W466R, W478R, W493R

Other names

Canonical SPDI

NC_000009.12:121321399:T:C

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA374750189 OMIM: 137350.0004 dbSNP: rs2062427908 VarSome

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
Gene	OMIM	HI score Help 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.
GSN		-	-	GRCh38 GRCh37	977	1021

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 Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Finnish type amyloidosis	Uncertain significance (3)	criteria provided, multiple submitters, no conflicts	Nov 15, 2020	RCV001265608.8

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.	Expand all rows Collapse all rows 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.
Uncertain significance (Nov 15, 2020) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Finnish type amyloidosis (Autosomal dominant inheritance)	Department of Ophthalmology, Flinders Medical Centre Accession: SCV001443151.2 First in ClinVar: Nov 21, 2020 Last updated: Jun 10, 2023	Publications: PubMed (1) PubMed: 33973672 Observation: 1 Collection method: research Allele origin: unknown Affected status: yes Observation 1 Collection method: research Allele origin: unknown Affected status: yes

Uncertain significance (Apr 28, 2020) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Finnish type amyloidosis (Autosomal dominant inheritance)	Genetics and Molecular Pathology, SA Pathology Accession: SCV001981655.4 First in ClinVar: Oct 25, 2021 Last updated: Jul 14, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Pathogenic (May 17, 2024) N Not contributing to aggregate classification	no assertion criteria provided	AMYLOIDOSIS, FINNISH TYPE	OMIM Accession: SCV004028542.2 First in ClinVar: Aug 26, 2023 Last updated: May 26, 2024	Publications: PubMed (1) PubMed: 33973672 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: In a father, son, and daughter from an Australian family with Finnish-type amyloidosis (105120), Mullany et al. (2021) identified a c.1477T-C transition (c.1477T-C, NM_000177.5) in … (more) In a father, son, and daughter from an Australian family with Finnish-type amyloidosis (105120), Mullany et al. (2021) identified a c.1477T-C transition (c.1477T-C, NM_000177.5) in the GSN gene, resulting in a trp493-to-arg (W493R) substitution at a highly conserved residue. This variant was not present in public variant databases. The W93R variant was the first to be located in the G4 domain. Immunohistochemical studies on corneal tissue from the proband identified gelsolin protein within histologically defined corneal amyloid deposits. (less)

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
A novel GSN variant outside the G2 calcium-binding domain associated with Amyloidosis of the Finnish type.	Mullany S	Human mutation	2021	PMID: 33973672

Text-mined citations for rs2062427908 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Jul 15, 2026