ClinVar Miner

Submissions for variant NM_004999.4(MYO6):c.188-3T>C

gnomAD frequency: 0.00017  dbSNP: rs373199401
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Total submissions: 7
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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 RCV000218607 SCV000270539 likely benign not specified 2015-02-06 criteria provided, single submitter clinical testing c.188-3T>C in intron 3 of MYO6: This variant is not expected to have clinical si gnificance because it does not cause the splice site sequence to diverge from co nsensus. It has been identified in 15/67345 European chromosomes by the Exome Ag gregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs373199401).
Illumina Laboratory Services, Illumina RCV000322634 SCV000465354 uncertain significance Autosomal recessive nonsyndromic hearing loss 37 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina RCV000379547 SCV000465355 uncertain significance Autosomal dominant nonsyndromic hearing loss 22 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV001574138 SCV001800899 likely benign not provided 2020-12-21 criteria provided, single submitter clinical testing
Invitae RCV001574138 SCV002226551 uncertain significance not provided 2022-09-26 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with MYO6-related conditions. 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. ClinVar contains an entry for this variant (Variation ID: 227673). This variant is present in population databases (rs373199401, gnomAD 0.03%). This sequence change falls in intron 3 of the MYO6 gene. It does not directly change the encoded amino acid sequence of the MYO6 protein. It affects a nucleotide within the consensus splice site.
AiLife Diagnostics, AiLife Diagnostics RCV001574138 SCV002501761 uncertain significance not provided 2021-07-23 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004530305 SCV004751299 likely benign MYO6-related disorder 2019-06-06 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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