Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Lupski Lab, |
RCV000203292 | SCV000256760 | likely pathogenic | Myofibromatosis, infantile, 1 | 2013-02-12 | criteria provided, single submitter | research | This mutation has been found in two myofibromas from one of the affected familial cases. |
Demoulin lab, |
RCV000454371 | SCV000494643 | pathogenic | Infantile myofibromatosis | 2017-02-01 | criteria provided, single submitter | research | This mutation was found in two patients with myofibromatosis in our cohort and has been reported by others. It strongly activates PDGFRB signaling in cell culture (gain of function). It was associated with other mutations in the same gene: in one patient, it was associated with c.1696T>C (p.W566R) and in a second case, with c.1681C>T (p.R561C). Another variant, c.1998C>G, leads to the same amino acid change (p.N666K). |
Seattle Children's Hospital Molecular Genetics Laboratory, |
RCV002254286 | SCV002525700 | pathogenic | not provided | 2022-01-21 | criteria provided, single submitter | clinical testing | The PDGFRB p.Asn666Lys variant has been previously reported in the somatic state in multiple patients with infantile myofibromatosis (OMIM #228550) (PMID: 28334876 and others). The p.Asn666Lys variant is in the N-terminal lobe of the kinase domain of the PDGFRB protein and results in constitutive activation of downstream signaling (PMID: 28334876). This variant was identified in 35% of reads, suggesting somatic origin. Although the p.Asn666Lys variant has only been reported in the somatic state, constitutional activating variants in PDGFRB have been previously reported (PMID: 28334876 and others). |