ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.5899C>T (p.Arg1967Ter) (rs376764423)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000844723 SCV000204929 pathogenic Rare genetic deafness 2014-07-14 criteria provided, single submitter clinical testing The Arg1967X variant in MYO7A has been previously reported in one individual wit h Usher syndrome who was homozygous, and three affected family members were also found to be homozygous for the variant (Shahzad 2013). This variant has also be en identified in 1/8354 European American chromosomes by the NHLBI Exome Sequenc ing Project (; dbSNP rs376764423). Although this var iant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This nonsense variant leads to a premature termination codon at position 1967, which is predicted to lead to a tr uncated or absent protein. In summary, this variant meets our criteria to be cla ssified as pathogenic (
Illumina Clinical Services Laboratory,Illumina RCV000319894 SCV000374493 likely pathogenic MYO7A-Related Disorders 2016-06-14 criteria provided, single submitter clinical testing The c.5899C>T (p.Arg1967Ter) stop-gained variant has been reported in three studies in patients with Usher syndrome and is found in four affected siblings from a consanguineous family in a homozygous state, in one patient in a compound heterozygous state, and in one patient in a heterozygous state who also carried a second missense variant, but the phase is unknown (Shahzad et al. 2013; Bujakowska et al. 2014; Ellingford et al. 2016). The variant is also found in one unaffected parent in a heterozygous state (Bujakowska et al. 2014). One affected relative from the extended consanguineous family did not carry the p.Arg1967Ter variant. The variant was absent from 190 controls (Shahzad et al. 2013) but is reported at a frequency of 0.00005 in the European (Non-Finnish) population of the Exome Aggregation Consortium. Based on the evidence in the literature and the potential impact of stop-gained variants, the p.Arg1967Ter variant is classified as likely pathogenic for MYO7A-related disorders.
Centre for Genomic Medicine, Manchester,Central Manchester University Hospitals RCV000225571 SCV000282593 likely pathogenic Retinal dystrophy no assertion criteria provided clinical testing
Counsyl RCV000155243 SCV000487452 likely pathogenic Usher syndrome type 1 2016-11-10 no assertion criteria provided clinical testing
Counsyl RCV000411148 SCV000487453 likely pathogenic Deafness, autosomal recessive 2 2016-11-10 no assertion criteria provided clinical testing

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