ClinVar Miner

Submissions for variant NM_006019.4(TCIRG1):c.1718A>G (p.Glu573Gly)

gnomAD frequency: 0.00001  dbSNP: rs576389893
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002541709 SCV003471193 uncertain significance not provided 2022-02-10 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 573 of the TCIRG1 protein (p.Glu573Gly). This variant is present in population databases (rs576389893, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with TCIRG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 991177). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Neuberg Centre For Genomic Medicine, NCGM RCV001279347 SCV005382396 uncertain significance Autosomal recessive osteopetrosis 1 2023-05-20 criteria provided, single submitter clinical testing The observed missense c.1718A>G(p.Glu573Gly) variant in TCIRG1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is present with an allele frequency of 0.008% in gnomAD Exomes database. This variant has been reported to the ClinVar database as Uncertain significance. Multiple lines of computational evidence (Polyphen - probably damaging , SIFT - damaging and MutationTaster -disease causing) predict a damaging effect on protein structure and function for this variant. The amino acid change p.Glu573Gly in TCIRG1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Glu at position 573 is changed to a Gly changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as Uncertain Significance (VUS).
Natera, Inc. RCV001279347 SCV001466435 uncertain significance Autosomal recessive osteopetrosis 1 2020-04-16 no assertion criteria provided clinical testing

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