Submissions for variant GRCh38/hg38 17p12(chr17:16018139-16028011)x0

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV003327664	SCV004034162	pathogenic	Mitochondrial complex III deficiency nuclear type 2	2023-08-24	criteria provided, single submitter	research	A homozygous deletion of exons 8-10 in TTC19 (NM_017775.4) was identified by exome sequencing and confirmed by genome sequencing in two siblings with mitochondrial complex III deficiency ([GRCh 38] chr17:16018139_16028011x0). Inheritance information is unavailable. The patient phenotypes are nonspecific, but are consistent with cases described in the literature and/or published databases with overlapping variants. There is overlap with the 3’ end of the TTC19 gene including coding sequence. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of TTC19 is an established disease mechanism in autosomal recessive mitochondrial complex III deficiency (https://search.clinicalgenome.org/kb/gene-dosage). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive mitochondrial complex III deficiency. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1: 0 points, 2: 0.9 points, 3: 0 points, 4-5: 0.15 points; Total: 1.05 points; Riggs 2020 (PMID: 31690835).