ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.3546C>A (p.Asn1182Lys) (rs1555090294)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV000505067 SCV001164254 likely pathogenic Usher syndrome 2019-10-22 reviewed by expert panel curation The p.Asn1182Lys variant in MYO7A has been detected in 2 patients with Usher syndrome (PM3; PMID: 27460420, 28041643). One patient was homozygous for the variant, while the other was compound heterozygous with a likely pathogenic variant. The p.Asn1182Lys variant was absent from large population studies (PM2; At least one patient with a variant identified in this gene displayed sensorineural hearing loss and retinitis pigmentosa, features consistent with Usher syndrome (PP4). The REVEL computational prediction analysis tool produced a score of 0.833, which is above the threshold necessary to apply PP3; however, this information is not predictive of pathogenicity on its own (PP3). In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Usher syndrome. ACMG/AMP Criteria applied, as specified by the Hearing Loss Expert Panel: PM2, PM3, PP3, PP4.
Counsyl RCV000670174 SCV000795000 uncertain significance Deafness, autosomal recessive 2; Usher syndrome type 1 2017-10-24 criteria provided, single submitter clinical testing
Invitae RCV001047383 SCV001211338 uncertain significance not provided 2019-11-26 criteria provided, single submitter clinical testing This sequence change replaces asparagine with lysine at codon 1182 of the MYO7A protein (p.Asn1182Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of Usher syndrome (PMID: 27460420, 28041643, Invitae). ClinVar contains an entry for this variant (Variation ID: 438177). 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: Probably 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.
NIHR Bioresource Rare Diseases, University of Cambridge RCV000505067 SCV000599120 likely pathogenic Usher syndrome 2015-01-01 no assertion criteria provided research

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