ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.4739A>G (p.Tyr1580Cys)

gnomAD frequency: 0.00006  dbSNP: rs370232066
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Total submissions: 11
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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 RCV000036161 SCV000059813 uncertain significance not specified 2010-09-29 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Tyr1580Cys vari ant in MYO7A has not been reported in the literature nor previously identified b y our laboratory. The Tyrosine (Tyr) residue at position 1580 is conserved acros s mammals and some lower species and computational analyses (PolyPhen, SIFT, Ali gnGVGD) suggest that the Tyr1580Cys variant may impact the protein. However, thi s information is not predictive enough to assume pathogenicity. It should be not ed that this lab has only sequenced the MYO7A in approximately 200 individuals s uch that the full spectrum of benign variation has not yet been defined for this gene, increasing the possibility that this could be a benign variant. In summar y, the clinical significance of this variant cannot be determined with certainty at this time.
Illumina Laboratory Services, Illumina RCV001109030 SCV001266335 uncertain significance Autosomal dominant nonsyndromic hearing loss 11 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 RCV001114663 SCV001272565 uncertain significance Autosomal recessive nonsyndromic hearing loss 2 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 RCV001114664 SCV001272566 uncertain significance Usher syndrome type 1 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.
Invitae RCV001246336 SCV001419682 uncertain significance not provided 2022-10-03 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 1580 of the MYO7A protein (p.Tyr1580Cys). This variant is present in population databases (rs370232066, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with MYO7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 43256). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYO7A protein function. 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.
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center RCV001375116 SCV001572029 uncertain significance Hearing impairment 2021-04-12 criteria provided, single submitter clinical testing PM5_Moderate, PP3_Supporting
GeneDx RCV001246336 SCV001795383 uncertain significance not provided 2023-03-02 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31260034)
Natera, Inc. RCV001271766 SCV001453192 uncertain significance Usher syndrome type 1B 2020-04-17 no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV001246336 SCV001921041 uncertain significance not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001246336 SCV001954803 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001246336 SCV001965176 uncertain significance not provided no assertion criteria provided clinical testing

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