ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.1996C>T (p.Arg666Ter)

gnomAD frequency: 0.00004  dbSNP: rs121965085
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000151490 SCV000199563 pathogenic Rare genetic deafness 2014-01-15 criteria provided, single submitter clinical testing The p.Arg666X variant in MYO7A has been reported in 4 individuals with Usher syn drome type I, 3 of whom carried a second MYO7A variant (Janecke 1999, Pennings 2 004, Ouyang 2005, Bonnet 2011). This variant has been identified in 4/110570 Eu ropean chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.bro adinstitute.org; dbSNP rs121965085), which is low enough to be consistent with a recessive carrier frequency. This nonsense variant leads to a premature termina tion codon at position 666, which is predicted to lead to a truncated or absent protein. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Usher syndrome. ACMG/AMP criteria applied: PVS1, PM2.
Counsyl RCV000669149 SCV000793867 pathogenic Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2017-09-01 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001091731 SCV001247933 pathogenic not provided 2017-11-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001091731 SCV001380306 pathogenic not provided 2023-12-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg666*) in the MYO7A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO7A are known to be pathogenic (PMID: 8900236, 25404053). This variant is present in population databases (rs121965085, gnomAD 0.004%). This premature translational stop signal has been observed in individuals with autosomal recessive Usher syndrome (PMID: 10094549, 15660226, 21569298). ClinVar contains an entry for this variant (Variation ID: 11860). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002490356 SCV002780346 pathogenic Autosomal dominant nonsyndromic hearing loss 11; Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2021-10-08 criteria provided, single submitter clinical testing
GeneDx RCV001091731 SCV003761949 pathogenic not provided 2023-01-26 criteria provided, single submitter clinical testing Nonsense 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: 25525159, 31589614, 36240775, 21569298, 33576163, 32531858, 10094549, 27246798, 27957503, 35955564, 35440622, 12786748, 15660226, 15043528, 28075205)
OMIM RCV000012635 SCV000032870 pathogenic Usher syndrome type 1B 2005-03-01 no assertion criteria provided literature only
Natera, Inc. RCV000012635 SCV002086596 pathogenic Usher syndrome type 1B 2020-07-21 no assertion criteria provided clinical testing

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