ClinVar Miner

Submissions for variant NM_007171.3(POMT1):c.2163C>A (p.Tyr721Ter) (rs138902646)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000176088 SCV000227686 pathogenic not provided 2016-09-01 criteria provided, single submitter clinical testing
GeneDx RCV000176088 SCV000890216 likely pathogenic not provided 2018-10-04 criteria provided, single submitter clinical testing The Y721X nonsense variant has been reported previously in both the compound heterozygous and homozygous state in individuals with POMT1-related disorders (Bouchet et al., 2007; Manzini et al., 2008). The Y721X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). This variant is predicted to cause loss of normal protein function through protein truncation as the last 27 amino acids of the protein are lost. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV000535678 SCV000649892 uncertain significance Limb-girdle muscular dystrophy-dystroglycanopathy, type C1; Congenital muscular dystrophy-dystroglycanopathy with mental retardation, type B1; Walker-Warburg congenital muscular dystrophy 2017-05-16 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the last exon of the POMT1 mRNA at codon 721 (p.Tyr721*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 27 amino acids of the POMT1 protein. This variant has been reported in the literature in the heterozygous state in one individual affected with a fetal form of lissencephaly II in combination with another likely pathogenic variant (PMID: 17559086). It has also been reported in the homozygous state in an individual affected with Walker Warburg syndrome (WWS) (PMID: 18752264). ClinVar contains an entry for this variant (Variation ID: 195505). In summary, this variant deletes the last amino acids of the gene and it has been reported in affected individuals. However, additional genetic and/or functional evidence is necessary to classify this variant conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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