Submissions for variant NM_000260.4(MYO7A):c.803A>G (p.Lys268Arg)

gnomAD frequency: 0.00098  dbSNP: rs184866544

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155225	SCV000204911	likely benign	not specified	2015-05-17	criteria provided, single submitter	clinical testing	p.Lys268Arg in exon 8 of MYO7A: This variant was reported in one individual with Usher syndrome type 2 but did not segregate in an affected sibling (Bonnet 2011 ). In addition, this variant was identified in 0.2% (100/53924) of European chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs184866544). Furthermore, the lysine (Lys) residue at this position is not conserved in mammals and evolutionary distant species with two mammals, hor se and dolphin, having an arginine (Arg) at this position. In summary, this vari ant is not expected to have clinical significance based on lack of segregation w ith disease, the frequency of the variant in the general population, and conserv ation data.
Eurofins Ntd Llc (ga)	RCV000724234	SCV000232497	uncertain significance	not provided	2014-11-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000724234	SCV001148372	uncertain significance	not provided	2019-08-01	criteria provided, single submitter	clinical testing
Invitae	RCV000724234	SCV001209819	likely benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001112307	SCV001269958	likely benign	Autosomal dominant nonsyndromic hearing loss 11	2017-04-27	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV001112308	SCV001269959	uncertain significance	Autosomal recessive nonsyndromic hearing loss 2	2017-04-27	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 Laboratory Services, Illumina	RCV001112309	SCV001269960	uncertain significance	Usher syndrome type 1	2017-04-27	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.
GeneDx	RCV000724234	SCV001825754	uncertain significance	not provided	2020-10-28	criteria provided, single submitter	clinical testing	Reported in published literature in an individual with Usher syndrome who was also heterozygous for a pathogenic variant in the USH2A gene, but was not present in an affected sibling (Bonnet et al., 2011); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30245029, 21569298, 25262649)
PreventionGenetics, part of Exact Sciences	RCV003937457	SCV004749439	likely benign	MYO7A-related condition	2021-08-19	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).