Submissions for variant NM_024105.4(ALG12):c.931C>T (p.Arg311Cys) (rs746215829)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000432212	SCV000512017	uncertain significance	not provided	2018-10-04	criteria provided, single submitter	clinical testing	The R311C variant has been reported previously, in the compound heterozygous state with another missense variant, in a patient with congenital disorder of glycosylation type Ig (CDG-Ig) (Eklund et al., 2005). Although complementation studies demonstrated that wild-type hALG12 was able to correct the biochemical phenotype in fibroblast cells from the affected individual, functional analysis specifically showing pathogenicity of the R311C variant was not performed and additional studies are needed to validate the functional effect of this specific variant in vivo (Eklund et al., 2005). The R311C variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common variant in these populations. The R311C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is well conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore based on the information available at this time, we interpret R311C as a variant of unclear clinical significance.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic	RCV000660616	SCV000782734	uncertain significance	ALG12-congenital disorder of glycosylation	2017-09-21	criteria provided, single submitter	clinical testing
Fulgent Genetics,Fulgent Genetics	RCV000660616	SCV000896984	uncertain significance	ALG12-congenital disorder of glycosylation	2018-10-31	criteria provided, single submitter	clinical testing