Submissions for variant NM_013339.4(ALG6):c.1246_1250del (p.Leu416fs)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV003400361	SCV004111707	likely pathogenic	ALG6-related disorder	2023-10-11	criteria provided, single submitter	clinical testing	The ALG6 c.1246_1250del5 variant is predicted to result in a frameshift and premature protein termination (p.Leu416Valfs*73). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in ALG6 are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Baylor Genetics	RCV003459858	SCV004199118	likely pathogenic	ALG6-congenital disorder of glycosylation 1C	2023-10-09	criteria provided, single submitter	clinical testing
Invitae	RCV003459858	SCV004465505	pathogenic	ALG6-congenital disorder of glycosylation 1C	2023-05-23	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu416Valfs*73) in the ALG6 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 92 amino acid(s) of the ALG6 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ALG6-related conditions. This variant disrupts a region of the ALG6 protein in which other variant(s) (p.Ser478Pro) have been determined to be pathogenic (PMID: 10914684). 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.