Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000366837 | SCV000343266 | likely pathogenic | not provided | 2018-07-10 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV000600696 | SCV000731947 | likely pathogenic | Visceral heterotaxy | 2018-01-24 | criteria provided, single submitter | clinical testing | The p.Trp401X (NM_147191.1 c.1203G>A) variant in MMP21 has been previously repor ted in compound heterozygous dizygotic twins with heterotaxy (Guimier 2015). It has also been reported in ClinVar (Variation ID#289001). This variant has been i dentified in 0.035% (12/34418) of Latino chromosomes by the Genome Aggregation D atabase (http://gnomad.broadinstitute.org; rs137955225). Although this variant h as been seen in the general population, its frequency is low enough to be consis tent with a recessive carrier frequency. This nonsense variant leads to a premat ure termination codon at position 401, which is predicted to lead to a truncated or absent protein. Biallelic loss of function of the MMP21 gene has been associ ated with heterotaxy. In summary, although additional studies are required to fu lly establish its clinical significance, the p.Trp401X variant is likely pathoge nic for heterotaxy in an autosomal recessive manner based on its occurrence in a ffected individuals and predicted impact on the protein. |