Submissions for variant NM_000460.4(THPO):c.356G>A (p.Arg119His)

gnomAD frequency: 0.00038  dbSNP: rs143216798

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000178771	SCV000230925	uncertain significance	not provided	2015-01-17	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001150651	SCV001311739	likely benign	Thrombocythemia 1	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae	RCV000178771	SCV003449689	uncertain significance	not provided	2023-01-01	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 119 of the THPO protein (p.Arg119His). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt THPO protein function. ClinVar contains an entry for this variant (Variation ID: 197671). This variant has not been reported in the literature in individuals affected with THPO-related conditions. This variant is present in population databases (rs143216798, gnomAD 0.1%).
Ambry Genetics	RCV002516780	SCV003686557	uncertain significance	Inborn genetic diseases	2021-07-21	criteria provided, single submitter	clinical testing	The c.356G>A (p.R119H) alteration is located in exon 5 (coding exon 4) of the THPO gene. This alteration results from a G to A substitution at nucleotide position 356, causing the arginine (R) at amino acid position 119 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.