ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.3659C>T (p.Pro1220Leu) (rs727504710)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000155994 SCV000205706 uncertain significance not specified 2016-06-23 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Pro1220Leu va riant in MYO7A has been reported in 1 Caucasian individual with Usher syndrome w ho also had 2 variants in the USH2A gene sufficient to explain disease and in 1 individual by our laboratory who was also heterozygous for 2 pathogenic variants in 2 different genes (Bonnet 2011, LMM unpublished data). This variant has been identified in 1/9144 European chromosomes by the Exome Aggregation Consortium ( ExAC, http://exac.broadinstitute.org; dbSNP rs727504710). Computational predicti on tools and conservation analyses suggest that this variant may impact the prot ein, though this information is not predictive enough to determine pathogenicity . In summary, while the clinical significance of the p.Pro1220Leu variant is unc ertain, its presence in previously reported affected individuals who had alterna te explanations for the hearing loss suggests a more likely benign role for this variant.
Mendelics RCV000988611 SCV001138390 uncertain significance Deafness, autosomal recessive 2 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV001054597 SCV001218940 uncertain significance not provided 2019-12-17 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1220 of the MYO7A protein (p.Pro1220Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs727504710, ExAC 0.01%). This variant has not been reported in the literature in individuals with MYO7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 179208). 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 RCV001113006 SCV001270731 uncertain significance Usher syndrome type 1 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV000988611 SCV001270732 uncertain significance Deafness, autosomal recessive 2 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001113007 SCV001270733 uncertain significance Deafness, autosomal dominant 11 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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