Submissions for variant NC_000015.9:g.(?_89828307)_(89876985_?)del

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV004582930	SCV005064009	pathogenic	Fanconi anemia	2023-11-13	criteria provided, single submitter	clinical testing	This variant is a gross deletion of the genomic region encompassing exon(s) 18-38 of the FANCI gene, which includes the termination codon. This deletion extends beyond the assayed region for this gene and therefore may encompass additional genes. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to alter mRNA translation or result in a truncated protein product. This variant has not been reported in the literature in individuals affected with FANCI-related conditions. This variant disrupts a region of the FANCI protein in which other variant(s) (p.Arg1299*) have been determined to be pathogenic (PMID: 17452773, 17460694; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV004582929	SCV005064060	pathogenic	Progressive sclerosing poliodystrophy	2023-11-13	criteria provided, single submitter	clinical testing	A gross deletion of the genomic region encompassing the full coding sequence of the POLG gene has been identified. Loss-of-function variants in POLG are known to be pathogenic (PMID: 18546365). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. Isolated whole-gene deletions of POLG have not been reported in the literature. However, larger copy number events that include this gene have been reported (PMID: 23430898). For these reasons, this variant has been classified as Pathogenic.