Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000601577 | SCV000731964 | likely pathogenic | Complement component 5 deficiency | 2017-09-09 | criteria provided, single submitter | clinical testing | The p.Val1446TrpfsX19 (NM_001735.2 c.4336delG) variant in C5 has not been report ed in individuals with complement component 5 deficiency and was absent from lar ge population studies. This variant is predicted to cause a frameshift, which al ters the protein?s amino acid sequence beginning at position 1446 and leads to a premature termination codon 19 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Biallelic loss of function o f the C5 gene is an established disease mechanism in complement component 5 defi ciency. In summary, although additional studies are required to fully establish its clinical significance, the p.Val1446TrpfsX19 variant is likely pathogenic fo r complement component 5 deficiency in an autosomal recessive manner based upon a predicted impact to the protein. |