ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.5573T>C (p.Leu1858Pro) (rs368657015)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036193 SCV000059845 pathogenic Rare genetic deafness 2016-08-23 criteria provided, single submitter clinical testing The p.Leu1858Pro variant in MYO7A has been reported in at least 10 probands with Usher syndrome who were either homozygous for the variant or compound heterozyg ous with a second pathogenic or likely pathogenic variant in MYO7A (Bharadwaj 20 00, Roux 2006, Jacobson 2008, Blanchet 2007, Roux 2011, LeQuesne Stabej 2012, LM M data). It has been identified in 3/55658 European chromosomes by the Exome Agg regation Consortium (; dbSNP rs368657015), which is low enough to be consistent with the carrier frequency in the general populat ion. In summary, this variant meets criteria to be classified as pathogenic for Usher syndrome in an autosomal recessive manner based on its presence in homozyg osity or compound heterozygosity with a second pathogenic allele in many individ uals with Usher syndrome, and low frequency in the general population.
Fulgent Genetics,Fulgent Genetics RCV000763283 SCV000893927 likely pathogenic Deafness, autosomal dominant 11; Deafness, autosomal recessive 2; Usher syndrome type 1 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000779082 SCV000915558 pathogenic MYO7A-Related Disorders 2017-09-14 criteria provided, single submitter clinical testing Variants in the MYO7A gene are known to cause MYO7A-related disorders, which include Usher syndrome and autosomal recessive and autosomal dominant forms of nonsyndromic hearing loss. The c.5573T>C (p.Leu1858Pro) variant has been identified in a compound heterozygous state in at least six affected individuals, including five with Usher syndrome type 1 and one with autosomal recessive nonsyndromic hearing loss (Roux et al. 2006; Jacobson et al. 2008; Roux et al. 2011; Le Quesne Stabej et al. 2012; Bademci et al. 2016). One additional individual with Usher syndrome type 1 was heterozygous for the p.Leu1858Pro variant and another missense variant, but the phase of the variants was unclear (Bharadwaj et al. 2000). The variant has not been reported in conjunction with autosomal dominant nonsyndromic hearing loss. The p.Leu1858Pro variant was absent from 2148 control chromosomes and is reported at a frequency of 0.000056 in the European (non-Finnish) population of the Genome Aggregation Database. Based on the collective evidence, the p.Leu1858Pro variant is classified as pathogenic for MYO7A-related disorders. Note: While the p.Leu1858Pro variant has not been reported in conjunction with autosomal dominant nonsyndromic hearing loss, disease risk cannot be ruled out. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001268401 SCV001447303 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Invitae RCV001268401 SCV001589412 pathogenic not provided 2020-10-02 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 1858 of the MYO7A protein (p.Leu1858Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs368657015, ExAC 0.005%). This variant has been observed in individual(s) with Usher syndrome (PMID: 10930322, 28944237, 22135276, 16679490). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 43288). 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). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000668342 SCV000792923 likely pathogenic Deafness, autosomal recessive 2 2017-07-24 no assertion criteria provided clinical testing
Natera, Inc. RCV001273514 SCV001456625 pathogenic Usher syndrome, type 1B 2020-09-16 no assertion criteria provided clinical testing
Clinical Genetics,Academic Medical Center RCV001268401 SCV001925511 likely pathogenic not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV001268401 SCV001954676 likely pathogenic not provided no assertion criteria provided clinical testing

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