Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000412603 | SCV000967593 | pathogenic | Combined immunodeficiency due to moesin deficiency | 2018-12-03 | criteria provided, single submitter | clinical testing | The p.Arg171Trp variant in MSN is absent from large population studies but has b een reported as hemizygous in 9 males from 7 families with clinical features of immunodeficiency. It was shown to be inherited from unaffected heterozygous moth ers for 5 of the probands and was confirmed de novo in one proband (Lagresle-Pey rou et al. 2016, Delmonte et al. 2017, Bradshaw et al. 2018, Broad Institute Rar e Genomes Project). In vitro functional studies (Lagresle-Peyrou et al. 2016), c omputational prediction tools and conservation analysis all support an impact to protein function. In summary, this variant meets criteria to be classified as p athogenic for immunodeficiency in an X-linked manner based upon case counts, de novo occurrence, absence from controls, functional evidence, and in silico predi ctors. ACMG/AMP Criteria applied: PS4_Moderate, PS2, PM2, PS3_Supporting, PP3. |
| Ce |
RCV001092797 | SCV001249454 | pathogenic | not provided | 2018-05-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001092797 | SCV002247487 | pathogenic | not provided | 2023-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 171 of the MSN protein (p.Arg171Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with X-linked moesin deficiency (PMID: 27405666, 28378256, 29556235). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 372154). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Studies have shown that this missense change alters MSN gene expression (PMID: 29556235). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000412603 | SCV000490227 | pathogenic | Combined immunodeficiency due to moesin deficiency | 2016-12-15 | no assertion criteria provided | literature only |