Submissions for variant NM_198252.3(GSN):c.1037G>A (p.Arg346Gln)

gnomAD frequency: 0.00004  dbSNP: rs372681751

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000343155	SCV000476990	uncertain significance	Finnish type amyloidosis	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Ambry Genetics	RCV002348120	SCV002645478	uncertain significance	Inborn genetic diseases	2024-08-05	criteria provided, single submitter	clinical testing	The c.1190G>A (p.R397Q) alteration is located in exon 9 (coding exon 9) of the GSN gene. This alteration results from a G to A substitution at nucleotide position 1190, causing the arginine (R) at amino acid position 397 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV000343155	SCV002775832	uncertain significance	Finnish type amyloidosis	2022-05-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002523733	SCV003260140	uncertain significance	not provided	2024-09-09	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 397 of the GSN protein (p.Arg397Gln). This variant is present in population databases (rs372681751, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with GSN-related conditions. ClinVar contains an entry for this variant (Variation ID: 364807). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt GSN protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.