TABLE 2.
GLIALCAM variants found in MLC patients.
| Exon/Intron | DNA | Protein | Variant type | Pathogenicity (ACMG guidelines) | References | Extra info |
|---|---|---|---|---|---|---|
| 1 | c.68T>A | p.(Leu23His) | Missense | Likely pathogenic | Lopez-Hernandez et al. (2011a) | Signal peptide variant, abolishes protein expression (Arnedo et al., 2014a) |
| 2 | c.128T>A | p.(Ile43Asn) | Missense | Variant of unknown significance | This paper | |
| 2 | c.166C>T | p.(Gln56*) | Nonsense | Likely Pathogenic | Arnedo et al. (2014b) | Discussed in section 3.2.1 |
| 2 | c.167A>C | p.(Gln56Pro) | Missense | Variant of unknown significance | Arnedo et al. (2014b) | Functional experiments show incorrect junctional localization and normal homo-oligomerization (Arnedo et al., 2014a; Elorza-Vidal et al., 2020). Discussed in section 3.2.1 |
| 2 | c.176G>A | p.(Ser59Asn) | Missense | Pathogenic | van der Knaap et al. (2012) | Functional experiments show incorrect junctional localization and normal homo-oligomerization (Elorza-Vidal et al., 2020) |
| 2 | c.203A>T | p.(Lys68Met) | Missense | Pathogenic | Cao et al. (2016), Shi et al. (2019) | |
| 2 | c.204G>C | p.(Lys68Asn) | Missense | Variant of unknown significance | This paper | |
| 2 | c.217C>T | p.(Arg73Trp) | Missense | Variant of unknown significance | Arnedo et al. (2014b) | Functional experiments show normal junctional localization (Arnedo et al., 2014b). Discussed in section 3.2.1 |
| 2 | c.265G>A | p.(Gly89Ser) | Missense | Pathogenic | Lopez-Hernandez et al. (2011a) | Functional experiments show incorrect junctional localization and impaired homo-oligomerization (Arnedo et al., 2014a) |
| 2 | c.265G>C | p.(Gly89Arg) | Missense | Likely Pathogenic | This paper | |
| 2 | c.266G>A | p.(Gly89Asp) | Missense | Pathogenic | Lopez-Hernandez et al. (2011a) | Functional experiments show incorrect junctional localization and impaired homo-oligomerization (Lopez-Hernandez et al., 2011a; Lopez-Hernandez et al., 2011b; Arnedo et al., 2014a) |
| 2 | c.274C>T | p.(Arg92Trp) | Missense | Pathogenic | Lopez-Hernandez et al. (2011a), Cao et al. (2016), Shi et al. (2019) | Functional experiments show incorrect junctional localization and impaired homo-oligomerization (Lopez-Hernandez et al., 2011a; Lopez-Hernandez et al., 2011b; Arnedo et al., 2014a). Discussed in section 3.2.1section .2.1 and 3.5 |
| 2 | c.275G>A | p.(Arg92Gln) | Missense | Pathogenic | Lopez-Hernandez et al. (2011a) | Functional experiments show incorrect junctional localization and impaired homo-oligomerization (Lopez-Hernandez et al., 2011a; Lopez-Hernandez et al., 2011b; Arnedo et al., 2014a) |
| 2 | c.275G>C | p.(Arg92Pro) | Missense | Likely Pathogenic | Shi et al. (2019) | Discussed in section 3.2.1 |
| 2 | c.292C>T | p.(Arg98Cys) | Missense | Pathogenic | Lopez-Hernandez et al. (2011a) | Functional experiments show incorrect junctional localization and impaired homo-oligomerization (Lopez-Hernandez et al., 2011a; Lopez-Hernandez et al., 2011b; Arnedo et al., 2014a) |
| 2 | c.293G>A | p.(Arg98His) | Missense | Pathogenic | Abdel-Salam et al. (2016) | |
| 2 | c.298C>T | p.(Arg100*) | Nonsense | Pathogenic | This paper | |
| 2 | c.382G>A | p.(Asp128Asn) | Missense | Pathogenic | Lopez-Hernandez et al. (2011a) | Functional experiments show incorrect junctional localization and normal homo-oligomerization (Arnedo et al., 2014a). Discussed in section 3.2.3 |
| 2 | c.395C>A | p.(Thr132Asn) | Missense | Pathogenic | Cao et al. (2016), Abbink et al. (2019) | |
| 2 | c.397G>A | p.(Gly133Arg) | Missense | Variant of unknown significance | This paper | |
| 2 | c.404_406del | p.(Lys135del) | In frame deletion | Pathogenic | Lopez-Hernandez et al. (2011a) | Functional experiments show normal junctional localization and normal homo-oligomerization (Arnedo et al., 2014a) |
| 3 | c.442C>T | p.(Pro148Ser) | Missense | Pathogenic | Lopez-Hernandez et al. (2011a) | Functional experiments show normal junctional localization and normal homo-oligomerization (Arnedo et al., 2014a) |
| 3 | c.461_462del | p.(Ser154Tyrfs*17) | Frameshift | Pathogenic | Lopez-Hernandez et al. (2011a) | Discussed in section 3.2.3 |
| 3 | c.580_582delinsTT | p.(Leu194Phefs*61) | Frameshift | Likely Pathogenic | Lopez-Hernandez et al. (2011a) | |
| 3 | c.587C>A | p.(Ser196Tyr) | Missense | Pathogenic | Lopez-Hernandez et al. (2011a) | Functional experiments show normal junctional localization and normal homo-oligomerization (Lopez-Hernandez et al., 2011a; Lopez-Hernandez et al., 2011b) |
| 3 | c.631G>A | p.(Asp211Asn) | Missense | Pathogenic | Lopez-Hernandez et al. (2011a) | Functional experiments show normal junctional localization (Arnedo et al., 2014a) |
| IVS3 | c.710–2A>G | p.? | Splice defect | Likely Pathogenic | This paper | |
| 4 | c.742G>T | p.(Gly248*) | Nonsense | Pathogenic | Lopez-Hernandez et al. (2011a) | |
| 4 | c.789G>A | p.(Trp263*) | Nonsense | Pathogenic | Lopez-Hernandez et al. (2011a) | Functional experiments show reduced protein expression and disrupted plasma membrane localization (Arnedo et al., 2014a). Discussed in section 3.2.3 |
Variants in bold lettering are dominant variants that cause remitting MLC.