ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.401T>A (p.Ile134Asn) (rs111033181)

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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 RCV000036134 SCV000059786 likely pathogenic Rare genetic deafness 2011-03-25 criteria provided, single submitter clinical testing The Ile134Asn variant in MYO7A has been reported in one proband with Usher syndr ome Type I and was absent in 172 control chromosomes (Bharadwaj 2000). We have a lso observed this variant in another patient with Usher syndrome with a pathogen ic variant on the other allele. In addition, this residue is highly conserved ac ross species and computational analyses (biochemical amino acid properties, homo logy, PolyPhen2, SIFT) suggest that the variant may impact the protein. In summa ry, this data suggests this variant is likely pathogenic.
Counsyl RCV000673536 SCV000798748 likely pathogenic Deafness, autosomal recessive 2; Usher syndrome type 1 2018-03-23 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001074683 SCV001240276 pathogenic Retinal dystrophy 2019-03-21 criteria provided, single submitter clinical testing
Invitae RCV001231996 SCV001404537 uncertain significance not provided 2019-09-28 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with asparagine at codon 134 of the MYO7A protein (p.Ile134Asn). The isoleucine residue is highly conserved and there is a large physicochemical difference between isoleucine and asparagine. This variant is present in population databases (rs111033181, ExAC 0.006%). This variant has been observed in individuals affected with Usher syndrome (PMID: 26969326, 25468891). ClinVar contains an entry for this variant (Variation ID: 43230). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Clinical Services Laboratory,Illumina RCV001249698 SCV001423720 uncertain significance MYO7A-Related Disorders 2019-11-01 criteria provided, single submitter clinical testing The MYO7A c.401T>A (p.Ile134Asn) variant is a missense variant which has been reported in two studies in which it has been identified in a compound heterozygous state in two patients with Usher syndrome (Bujakowska et al. 2014; Sloan-Heggen et al. 2016). The p.Ile134Asn variant is reported at a frequency of 0.000062 in the European (non-Finnish) population of the Genome Aggregation Database in a region of good sequence coverage, suggesting that it is a rare variant. The p.Ile134Asn variant is highly conserved through evolution, and in silico tools predict the variant to be damaging for the protein function. Functional studies for the variant were not performed. Based on the limited evidence and application of the ACMG criteria, the p.Ile134Asn variant is classified as a variant of unknown significance for MYO7A-related disorders.

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