Table 3.
Summary of variant analyses
| Variant | Variant Type | 1KG / ESP (MAF)1 | Pathogenicity Predicitons2 | Reporter Gene Transactivation | Subcellular Localization | Variant Interpretation3 | Reference |
|---|---|---|---|---|---|---|---|
| p.Asp6GlufsX32 (c.18_19delinsA) | Frameshift | na / na | na | Decreased | na | Disease causing | This study |
| p.Gly17Cys (c.49G>T) | Missense | 0.002 / 0.003 | + + + + − | Normal | Normal | Variant of uncertain significance | This study; DeLuca et al. 2010 |
| p.Ala50ProfsX9 (c.148delG) | Frameshift | na / na | na | Decreased | na | Disease causing | Ma et al. 2011 |
| p.Ala53dup (c.157_159dupGCC) | Polyalanine expansion | na / na | na | Normal | Normal | Variant of uncertain significance | This study; D’Alessandro et al. 2013 |
| p.Ala52_Ala53dup (c.154_159dupGCCGCC) | Polyalanine expansion | na / na | na | Normal | Normal | Variant of uncertain significance | Wessels et al. 2010 |
| p.Ser109Cys (c.326C>G) | Missense | na / 0.0002 | + + na − − | Normal | Abnormal | Likely disease associated | This study |
| p.Glu155X (c.463G>T) | Nonsense | na / na | na | Decreased | Abnormal | Disease causing | This study |
| p.Tyr199delfsX19 (c.595-610del TACCGCCCAGTGGCCA) | Frameshift | na / na | na | Decreased | Abnormal | Disease causing | This study |
| p.Pro217Ala (c.649C>G) | Missense | 0.003 / 0.008 | − − + − + | Normal | Abnormal | Likely disease associated | This study; Ware et al. 2004 |
| p.Ser252X (c.755C>A) | Nonsense | na / na | na | Decreased | Abnormal | Disease causing | This study |
| p.Glu291GlyfsX53 (c.866dupG) | Frameshift | na / na | na | Decreased | Abnormal | Disease causing | This study |
| p.His318Asn (c.952C>A) | Missense | na / na | + + + + − | Decreased | Abnormal | Disease causing | This study |
| p.Arg350Gly (c.1048A>G) | Missense | na / na | + + + + + | Decreased | Abnormal | Disease causing | D’Alessandro et al. 2011 |
| p.Ser402Pro (c.1204T>C) | Missense | na / na | + + + + + | Normal | Abnormal | Disease causing | Ma et al. 2011 |
| p.Ala447Gly (c.1340C>G) | Missense | na / na | + + + + − | Increased | Abnormal | Disease causing | This study |
MAFs represent allele frequencies for the minor allele (in all populations) from the 1000 Genomes Project (1KG, http://www.1000genomes.org/) and NHLBI Exome Sequencing Project (ESP, http://evs.gs.washington.edu/EVS/) databases. 1KG data encompass whole genome indels and SNP variants from 1092 individuals representing 14 world-wide populations (20110521-V3), while ESP data encompass exome SNP variants from 6503 individuals of European American and African American descent (ESP6500SI-V2).
Missense variant pathogenicity predictions were generated using (from left to right) Polyphen (genetics.bwh.harvard.edu/pph2/), SIFT (sift.jcvi.org/), PANTHER (http://www.pantherdb.org/tools/csnpScoreForm.jsp), Mutation Taster (http://www.mutationtaster.org/), and PMut (http://mmb2.pcb.ub.es:8080/PMut/) algorithms. Variants were predicted to be damaging (+), or benign/neutral (−). Analyses which were not possible are also indicated (na).
Based on clinical molecular diagnostic laboratory guidelines (see Materials and Methods)