Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000825535 | SCV000966850 | likely pathogenic | Congenital microvillous atrophy | 2018-04-18 | criteria provided, single submitter | clinical testing | The p.Phe450Leufs variant in MYO5B has been reported in 1 individual with Microv illous inclusion disease and segregated in 1 affected sibling (Perry 2014) . It was absent from large population studies. This variant is predicted to cause a f rameshift, which alters the protein?s amino acid sequence beginning at position 450 and leads to a premature termination codon 30 amino acids downstream. This a lteration is then predicted to lead to a truncated or absent protein. In summary , although additional studies are required to fully establish its clinical signi ficance, the p.Phe450Leufs variant is likely pathogenic for Microvillus inclusio n disease in an autosomal recessive manner. ACMG/AMP Criteria applied: PVS1_Stro ng; PM2, PM3_Supporting. |
| Labcorp Genetics |
RCV001858399 | SCV002155694 | pathogenic | not provided | 2021-09-03 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individual(s) with microvillous inclusion disease (PMID: 25111220). This sequence change creates a premature translational stop signal (p.Phe450Leufs*30) in the MYO5B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO5B are known to be pathogenic (PMID: 18724368, 20186687). This variant is not present in population databases (ExAC no frequency). ClinVar contains an entry for this variant (Variation ID: 666977). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001858399 | SCV005324988 | likely pathogenic | not provided | 2024-03-14 | criteria provided, single submitter | clinical testing | Identified heterozygous in two siblings with diarrhea and villous atrophy on biopsy; each sibling also harbored a MYO5B polymorphism, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (PMID: 25111220); Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 29266534, 32583448, 25111220) |
| OMIM | RCV000825535 | SCV002520516 | pathogenic | Congenital microvillous atrophy | 2022-05-20 | no assertion criteria provided | literature only |