Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000485237 | SCV000568778 | likely pathogenic | not provided | 2016-10-13 | criteria provided, single submitter | clinical testing | The c.727_729delTCC variant in the MYH3 gene has been reported previously segregating in a family with distal arthrogryposis type 8 (Chong et al., 2015). The c.727_729delTCC variant causes an in-frame deletion of one amnio acid, Serine 243, denoted p.Ser243del. The c.727_729delTCC variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.727_729delTCC as a likely pathogenic variant. |
Clinical Genomics Laboratory, |
RCV000185628 | SCV005045075 | likely pathogenic | Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A | 2024-02-20 | criteria provided, single submitter | clinical testing | The MYH3 c.727_729del (p.Ser243del) variant has been reported in at least two unrelated individuals with contractures, pterygia, and spondylocarpotarsal fusion syndrome-1A and is reported to segregate with disease in three individuals in one family (Chong JX et al., PMID: 25957469; Zieba J et al., PMID: 28205585). This variant is absent from the general population (gnomAD v.2.1.1), indicating it is not a common variant. This variant is predicted to cause a change in the length of the protein due to an in-frame deletion of a serine residue in a non-repeat region. This variant has been reported in the ClinVar database as a germline pathogenic or likely pathogenic variant by three submitters. Based on available information and the ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), this variant is classified as likely pathogenic. |
OMIM | RCV000185628 | SCV000238540 | pathogenic | Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A | 2015-05-07 | no assertion criteria provided | literature only | |
University of Washington Center for Mendelian Genomics, |
RCV000185628 | SCV000281695 | pathogenic | Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A | 2015-05-19 | no assertion criteria provided | research | |
University of Washington Center for Mendelian Genomics, |
RCV000755065 | SCV000882883 | likely pathogenic | Spondylocarpotarsal synostosis syndrome | 2017-02-16 | no assertion criteria provided | research |