Submissions for variant NM_001206744.2(TPO):c.650A>G (p.Asn217Ser)

gnomAD frequency: 0.00009  dbSNP: rs148683218

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000339355	SCV000416661	uncertain significance	Deficiency of iodide peroxidase	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.
Genetics and Molecular Pathology, SA Pathology	RCV002272212	SCV002556492	uncertain significance	Hypothyroidism due to TSH receptor mutations	2020-05-08	criteria provided, single submitter	clinical testing	The TPO c.650A>G variant is classified as VUS The TPO c.650A>G variant is a single nucleotide change in exon Missing Exon of the TPO gene, which is predicted to change the amino acid asparagine at position 217 in the protein to serine. Population data not informative for path nor benign. Conflicting pathogenetic predictors, leaning towards benign. The variant has been reported in dbSNP (rs148683218) and has been reported as Uncertain significance by other diagnostic laboratories (ClinVar Variation ID: 331310). It has not been reported in HGMD. Very little information present, none definitive for either pathogenic nor benign.
PreventionGenetics, part of Exact Sciences	RCV003418047	SCV004117940	uncertain significance	TPO-related disorder	2023-08-11	criteria provided, single submitter	clinical testing	The TPO c.650A>G variant is predicted to result in the amino acid substitution p.Asn217Ser. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.021% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-1459885-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.