rs74315520
- Pathogenic
Your Genotype
Sign InDescription
The Q377X nonsense variant in the SOX10 gene has been reported previously in individuals with Waardenburg syndrome type 4 and additional neurological abnormalities (Southard-Smith et al., 1999). It has also been reported as an apparently de novo variant in an individual with PCWH syndrome (Oshimo et al., 2012). This variant is predicted to cause loss of normal protein function through protein truncation, as the last 90 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014). Published functional studies demonstrate a damaging effect on SOX10 function in certain transcriptional pathways (Chan et al., 2003; Yokoyama et al., 2006), and mouse models show an abnormal phenotype compared to wild-type mice (Truch et al., 2018). The Q377X variant is not observed in large population cohorts (Lek et al., 2016). In summary, we interpret this variant as pathogenic.
Reference Allele
G
Alternative Allele
A
Chromosome
22
Location
37973767
Variant Type
SNP
ClinVar
Name
NM_006941.4(SOX10):c.1129C>T (p.Gln377Ter)
Allele
A
Clinical Significance
Pathogenic