Submissions for variant NM_000260.4(MYO7A):c.2293C>A (p.Leu765Met)

gnomAD frequency: 0.00029  dbSNP: rs201203036

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036084	SCV000059736	uncertain significance	not specified	2018-08-09	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Leu765Met var iant in MYO7A has been previously identified by our laboratory in 5 individuals with hearing loss; however, a variant affecting the other copy of MYO7A was not identified in any of these individuals. This variant has also been reported in C linVar (Variation ID 43180) and has been identified in 56/121520 European chromo somes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.o rg). Computational prediction tools and conservation analysis do not provide sup port for or against an impact the protein. In summary, while the clinical signif icance of the p.Leu765Met variant is uncertain, its frequency suggests it is mor e likely to be benign. ACMG/AMP Criteria applied: BS1_Supporting.
Illumina Laboratory Services, Illumina	RCV000383860	SCV000374282	uncertain significance	Usher syndrome type 1	2018-01-13	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	RCV000270954	SCV000374283	likely benign	Autosomal dominant nonsyndromic hearing loss 11	2018-01-13	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000326027	SCV000374284	uncertain significance	Autosomal recessive nonsyndromic hearing loss 2	2018-01-13	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.
Eurofins Ntd Llc (ga)	RCV000727020	SCV000704986	uncertain significance	not provided	2017-02-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000727020	SCV001197756	likely benign	not provided	2024-12-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000727020	SCV001874925	uncertain significance	not provided	2024-01-25	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV004018785	SCV004953195	uncertain significance	Inborn genetic diseases	2022-01-05	criteria provided, single submitter	clinical testing	The c.2293C>A (p.L765M) alteration is located in exon 20 (coding exon 19) of the MYO7A gene. This alteration results from a C to A substitution at nucleotide position 2293, causing the leucine (L) at amino acid position 765 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV005003423	SCV005632226	uncertain significance	Autosomal dominant nonsyndromic hearing loss 11; Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1	2024-03-08	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001276689	SCV001463197	uncertain significance	Usher syndrome type 1B	2020-01-24	no assertion criteria provided	clinical testing