Submissions for variant NM_018006.5(TRMU):c.1073_1081dup (p.Gln358_Val360dup)

dbSNP: rs753112330

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000667762	SCV000792264	uncertain significance	Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	2017-06-20	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000734954	SCV000863135	uncertain significance	not provided	2018-08-22	criteria provided, single submitter	clinical testing
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000667762	SCV001150302	pathogenic	Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	2018-01-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000734954	SCV001231171	pathogenic	not provided	2024-02-24	criteria provided, single submitter	clinical testing	This variant, c.1073_1081dup, results in the insertion of 3 amino acid(s) of the TRMU protein (p.Gln358_Val360dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs753112330, gnomAD 0.008%). This variant has been observed in individual(s) with acute infantile liver failure (PMID: 21169334, 30369941, 33365252). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.1081_1082insAGGCTGTGC. ClinVar contains an entry for this variant (Variation ID: 552491). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000734954	SCV001786248	likely pathogenic	not provided	2021-04-02	criteria provided, single submitter	clinical testing	In-frame insertion of 3 amino acids in a non-repeat region; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 21169334, 30369941, 21153446, 25407320, 27854233)
MGZ Medical Genetics Center	RCV000667762	SCV002581896	uncertain significance	Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	2022-09-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003117469	SCV003801141	uncertain significance	not specified	2023-01-11	criteria provided, single submitter	clinical testing	Variant summary: TRMU c.1073_1081dupAGGCTGTGC (p.Gln358_Val360dup) results in an in-frame duplication that is predicted to duplicate three amino acids into the encoded protein. The variant allele was found at a frequency of 2e-05 in 251186 control chromosomes (gnomAD). c.1073_1081dupAGGCTGTGC has been reported in the literature in individuals affected with Leigh syndrome with liver failure (Theunissen_2018) and with defects in mitochondrial complexes I and IV (Schara_TRMU_JIMD_2010). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=3) and pathogenic /likely pathogenic (n=4). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Baylor Genetics	RCV003472090	SCV004204362	likely pathogenic	Aminoglycoside-induced deafness	2024-02-12	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005027792	SCV005663880	pathogenic	Aminoglycoside-induced deafness; Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	2024-02-06	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000667762	SCV002076163	likely pathogenic	Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins	2020-09-15	no assertion criteria provided	clinical testing