Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000013284 | SCV000914600 | pathogenic | Triosephosphate isomerase deficiency | 2018-12-17 | criteria provided, single submitter | clinical testing | The TPI1 c.315G>C (p.Glu105Asp) missense variant, which is also referred to as p.Glu104Asp, is a well-known and common disease-associated variant, accounting for approximately 80% of clinical triosephosphate isomerase (TPI) deficiency. Across a selection of the available literature, the p.Glu105Asp variant was observed in 19 patients with TPI deficiency, including 13 homozygotes and six compound heterozygotes (Daar et al. 1986; Schneider et al. 1995; Arya et al. 1997; Linarello et al. 1998; Valentin et al. 2000; Yenicesu et al. 2000; Fermo et al. 2010; Sarper et al. 2013). Rodriguez-Almazan et al. (2008) demonstrated that the p.Glu105Asp variant results in instability of the TPI dimer and causes dissociation of the protein into inactive monomers, while De La Mora-De La Mora et al. (2013) showed that the p.Glu105Asp variant increases enzyme susceptibility to proteolysis. The highest allele frequency reported for this variant in the Exome Aggregation Consortium database is 0.000150 in the non-Finnish European population. Based on the collective evidence, the TPI1 p.Glu105Asp variant is classified as pathogenic for triosephosphate isomerase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Laboratory for Molecular Medicine, |
RCV000013284 | SCV000967685 | pathogenic | Triosephosphate isomerase deficiency | 2018-12-17 | criteria provided, single submitter | clinical testing | The p.Glu142Asp (also known as p.Glu105Asp or p.Glu104Asp) variant in TPI1 has b een reported in at least 10 homozygous and 4 compound heterozygous individuals w ith triosephosphate isomerase deficiency (Aissa 2014, Alabdullatif 2017, Arya 19 97, Daar 1986, Nolan 2016, Pekrun 1995, Sarper 2013, Valentin 2000). It has als o been identified in 0.015% (19/129206) of European chromosomes by gnomAD (http: //gnomad.broadinstitute.org). In vitro functional studies and computational pred iction tools support an impact on protein function (Daar 1986, Ralser 2006, De L a Mora-De La Mora 2013). In summary, this variant meets criteria to be classifie d as pathogenic for autosomal recessive triosephosphate isomerase deficiency. AC MG/AMP criteria applied: PM3_VeryStrong, PS3_Moderate, PM2_Supporting, PP3. |
| Genomics Facility, |
RCV000013284 | SCV002073904 | likely pathogenic | Triosephosphate isomerase deficiency | 2021-12-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001851818 | SCV002240735 | pathogenic | not provided | 2023-06-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects TPI1 function (PMID: 17183658). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 12468). This missense change has been observed in individual(s) with triosephosphate isomerase deficiency (PMID: 2876430, 10910933, 24192681). This variant is present in population databases (rs121964845, gnomAD 0.01%). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 105 of the TPI1 protein (p.Glu105Asp). |
| Genetics and Molecular Pathology, |
RCV000013284 | SCV002556914 | pathogenic | Triosephosphate isomerase deficiency | 2021-08-17 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000013284 | SCV000033531 | pathogenic | Triosephosphate isomerase deficiency | 2008-08-22 | no assertion criteria provided | literature only |