Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV002221482 | SCV002498780 | benign | Mitochondrial disease | 2022-01-10 | reviewed by expert panel | curation | The m.7476C>T variant in MT-TS1 was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel as part of the variant pilot for mitochondrial DNA variant specifications (McCormick et al., 2020; PMID: 32906214). This variant is seen in 1.310% of individuals in the GenBank dataset (BA1), including in haplogroups J2a (99.7% of individuals) and J2b (98.85% of individuals). Furthermore, this variant is seen in the gnomAD dataset (v3.1.2) at an overall homoplasmic allele frequency of 1% including in haplogroup J at 20%. If an affected individual is not a member this haplogroup, further evaluation of the variant in that particular individual should be considered. The computational predictor MitoTIP suggests this variant does not impact the function of this tRNA with a score in the 20th percentile, as does HmtVar with a score of 0.1 (BP4). In summary, this variant meets criteria to be classified as benign. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel as of August 20, 2020. Mitochondrial DNA-specific ACMG/AMP criteria applied: BA1, BP4. |
Laboratory for Molecular Medicine, |
RCV000035053 | SCV000058693 | likely benign | not specified | 2013-10-16 | criteria provided, single submitter | clinical testing | m.7476C>T in MT-TS1: This variant is not expected to have clinical significance because it has been observed at equal frequencies in Caucasian individuals with hearing loss and in the general population (Houshmand 1994, Thomas 1996, Sternbe rg 1998, Li 2004, Konings 2008, mtDB-Human Mitochondrial Genome Database). |
Wong Mito Lab, |
RCV000850894 | SCV000993128 | benign | MELAS syndrome | 2019-07-12 | criteria provided, single submitter | clinical testing | The NC_012920.1:m.7476C>T variant in MT-TS1 gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS2, BP4 |