Submissions for variant NM_003235.5(TG):c.6001G>A (p.Asp2001Asn)

gnomAD frequency: 0.00037  dbSNP: rs199923962

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001165417	SCV001327607	uncertain significance	Iodotyrosyl coupling defect	2018-01-13	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.
GeneDx	RCV001529622	SCV002005594	uncertain significance	not provided	2019-04-29	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32428920)
Fulgent Genetics, Fulgent Genetics	RCV002483921	SCV002788222	uncertain significance	Iodotyrosyl coupling defect; Autoimmune thyroid disease, susceptibility to, 3	2022-05-18	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001529622	SCV005196124	uncertain significance	not provided		criteria provided, single submitter	not provided
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004768881	SCV005381709	uncertain significance	not specified	2024-08-27	criteria provided, single submitter	clinical testing	Variant summary: TG c.6001G>A (p.Asp2001Asn) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00024 in 251348 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in TG causing TG-Related Disorders, allowing no conclusion about variant significance. c.6001G>A has been reported in the literature in individuals affected with TG-Related Disorders. These report(s) do not provide unequivocal conclusions about association of the variant with TG-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 32428920). ClinVar contains an entry for this variant (Variation ID: 912286). Based on the evidence outlined above, the variant was classified as uncertain significance.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529622	SCV001743384	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001529622	SCV001975158	uncertain significance	not provided		no assertion criteria provided	clinical testing