NM_198252.3(GSN):c.1324T>C (p.Trp442Arg) AND Finnish type amyloidosis

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Nov 15, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001265608.8

Allele description [Variation Report for NM_198252.3(GSN):c.1324T>C (p.Trp442Arg)]

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

Gene:

GSN:gelsolin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q33.2

Genomic location:

Preferred name:

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

HGVS:

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

Protein change:

W224R; TRP493ARG

Links:

OMIM: 137350.0004; dbSNP: rs2062427908

Molecular consequence:

NM_000177.5:c.1477T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127662.2:c.1324T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127663.2:c.1432T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127664.2:c.1324T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127665.2:c.1324T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127666.2:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127667.2:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001258029.2:c.1375T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001258030.2:c.1348T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353053.1:c.1324T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353054.1:c.1324T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353055.2:c.1324T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353056.2:c.1324T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353057.2:c.1324T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353058.2:c.1324T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353059.2:c.1324T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353060.2:c.1324T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353061.2:c.1324T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353062.1:c.1324T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353063.2:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353064.2:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353065.2:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353066.2:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353067.2:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353068.2:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353069.2:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353070.2:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353071.2:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353072.2:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353073.2:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353074.2:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353075.1:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353076.2:c.1396T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353077.1:c.1357T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001353078.2:c.670T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_198252.3:c.1324T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Finnish type amyloidosis
Synonyms:: AMYLOID CRANIAL NEUROPATHY WITH LATTICE CORNEAL DYSTROPHY; AMYLOIDOSIS DUE TO MUTANT GELSOLIN; Lattice corneal dystrophy associated with familial systemic amyloidosis; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007097; MedGen: C1622345; Orphanet: 85448; OMIM: 105120

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001443151	Department of Ophthalmology, Flinders Medical Centre	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 15, 2020)	unknown	research	PubMed (2) [See all records that cite these PMIDs] 33973672, 25741868
SCV001981655	Genetics and Molecular Pathology, SA Pathology See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 28, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004028542	OMIM	no assertion criteria provided	Pathogenic (May 17, 2024)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001443151

Department of Ophthalmology, Flinders Medical Centre

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 15, 2020)

unknown

research

PubMed (2)
[See all records that cite these PMIDs]

SCV001981655

Genetics and Molecular Pathology, SA Pathology

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 28, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004028542

OMIM

no assertion criteria provided

Pathogenic
(May 17, 2024)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

A novel GSN variant outside the G2 calcium-binding domain associated with Amyloidosis of the Finnish type.

Mullany S, Souzeau E, Klebe S, Zhou T, Knight LSW, Qassim A, Berry EC, Marshall H, Hussey M, Dubowsky A, Breen J, Hassall MM, Mills RA, Craig JE, Siggs OM.

Hum Mutat. 2021 Jul;42(7):818-826. doi: 10.1002/humu.24214. Epub 2021 May 11.

PubMed [citation]

PMID:: 33973672

Details of each submission

From Department of Ophthalmology, Flinders Medical Centre, SCV001443151.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		not provided	not provided	not provided	research	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genetics and Molecular Pathology, SA Pathology, SCV001981655.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From OMIM, SCV004028542.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 14, 2026

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