Table 2 SORL1 variations. All SORL1 variations found to be likely pathogenic or of uncertain significance according to ACMG criteria [25] generated using three independent study cohorts
Chr:pos hg19 | Domain | Transcript Variant | Coding effect | Protein change | Predictions SIFT/MutTas | Prediction Splice-site effect MaxEnt/NNSPLICE/HSF | dbSNP ID | ExAC European Non-Finnish % | MAF % Case/Control EU EOD Swedes | Segregates with disease Family number | Classification ACMG | Study cohort |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
11:121340732 | VPS10p | c.302C > T (NM_003105.5) | Missense | p.Ser101Phe | Deleterious/Disease causing | −1.3% | – | – | 0.26/0 | Unknown FH | Uncertain sign. | case-control |
11:121383766 | VPS10p | c.994C > T (NM_003105.5) | Missense | p.Arg332Trp | Deleterious/Disease causing | None | rs772110877 | 0.01049 | 0.26/0 | Unknown FH | Uncertain sign. | case-control |
11:121391400 | VPS10p | c.1246C > T (NM_003105.5) | Nonsense | p.Arg416* | not applicable | −0.1% | rs144585461 | – | 0.26/0 | Unknown FH a | Likely path. | case-control |
11:121437647 | EGF | c.3050-2A < G (NM_003105.5) | Deletion | p.Gly1017-Glu1074del | not applicable | −100% | – | – | 0/0 | yes PED.27 | Likely path. | Targeted re-seq. |
11:121458821 | LDLR class A | c.3907C > T (NM_003105.5) | Missense | p.Arg1303Cys | Deleterious/Disease causing | None | rs781023219 | 0.005995 | 0/0 | yes PED.25 | Likely path. | WES-family |
11:121460051 | LDLR class A | c.4030 T > C (NM_003105.5) | Missense | p.Cys1344Arg | Deleterious/Disease causing | None | – | – | 0.26/0 | Possible FH b | Uncertain sign. | case-control |
11:121478841 | Fibronectin type III | c.5195G > C (NM_003105.5) | Missense | p.Gly1732Ala | Deleterious/Disease causing | None | rs777194720 | 0.007499 | 0.26/0 | yes PED.1499 | Uncertain sign. | case-control |