ClinVar Miner

Submissions for variant NM_000030.3(AGXT):c.866G>A (p.Arg289His) (rs61729604)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000587981 SCV000232896 uncertain significance not provided 2015-03-30 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587981 SCV000693981 uncertain significance not provided 2017-06-26 criteria provided, single submitter clinical testing Variant summary: The AGXT c.866G>A (p.Arg289His) variant involves the alteration of a non-conserved nucleotide and is predicted to be benign by 2/3 in silico tools. This variant was found in 24/16730 control chromosomes from ExAC at a frequency of 0.0014345, which does not exceed the estimated maximal expected allele frequency of a pathogenic AGXT variant (0.0023717). This variant has been reported as a part of two complex alleles in patients with Primary Hyperoxaluria Type 1 (Williams_2009, Williams_2015). The complex allele p.[Arg289His;Leu298Pro] was found in homozygous state in two related patients with the neonatal form of disease and another complex allele p.[Arg289His;Leu359Pro] was found in one patient in compound heterozygous state with c.33dupC. The role of this variant in the complex allele - whether it is a driver mutation or a modifier- has yet to be elucidated. In ClinVar while one laboratory has classified it as pathogenic, another laboratory has classified it as VUS. Another missense variant at the same residue (p.Arg289Cys) has been classified as a VUS by a lab in ClinVar. There are no functional studies for this variant, to our knowledge. Taken together, this variant is currently classified as 'Variant of Unknown Significance'.
Counsyl RCV000186341 SCV000800738 uncertain significance Primary hyperoxaluria, type I 2017-12-19 criteria provided, single submitter clinical testing
Invitae RCV000587981 SCV001110251 likely benign not provided 2019-02-08 criteria provided, single submitter clinical testing
Clinical Biochemistry Laboratory,Health Services Laboratory RCV000186341 SCV000239687 pathogenic Primary hyperoxaluria, type I 2014-11-27 no assertion criteria provided research

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