Submissions for variant NM_003235.5(TG):c.4481C>T (p.Pro1494Leu)

gnomAD frequency: 0.00052  dbSNP: rs146498231

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000361901	SCV000472050	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	RCV000413485	SCV000491916	uncertain significance	not provided	2018-06-14	criteria provided, single submitter	clinical testing	The P1494L variant in the TG gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. Although not present in the homozygous state, the NHLBI ESP Exome Sequencing Project reports P1494L was observed in 10/8600 alleles (0.12%) from individuals of European background, indicating it may be a rare variant in this population. The P1494L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved but in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P1494L as a variant of uncertain significance.
Fulgent Genetics, Fulgent Genetics	RCV002504182	SCV002815884	uncertain significance	Iodotyrosyl coupling defect; Autoimmune thyroid disease, susceptibility to, 3	2022-04-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000413485	SCV004163266	uncertain significance	not provided	2022-11-01	criteria provided, single submitter	clinical testing	TG: PM2, BP4