Submissions for variant NM_000260.4(MYO7A):c.449G>A (p.Arg150Gln)

gnomAD frequency: 0.00036  dbSNP: rs202245413

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000036149	SCV000059801	uncertain significance	not specified	2018-03-06	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Arg150Gln var iant in MYO7A has been previously identified by our laboratory in 3 individuals with hearing loss, none of whom carried a variant on the other copy of MYO7A. Fu rthermore, one of these individuals had a variant in a different gene that was s ufficient to explain their hearing loss. This variant has also been identified i n 0.05% (65/126624) of European chromosomes by the Genome Aggregation Database ( gnomAD, http://gnomad.broadinstitute.org; dbSNP rs202245413). Although this vari ant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation ana lysis suggest that the variant may not impact the protein, though this informati on is not predictive enough to rule out pathogenicity. In summary, while the cli nical significance of the p.Arg150Gln variant is uncertain, these data suggest t hat it is more likely to be benign. ACMG/AMP Criteria applied: BP4.
Fulgent Genetics, Fulgent Genetics	RCV000765012	SCV000896196	uncertain significance	Autosomal dominant nonsyndromic hearing loss 11; Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001109455	SCV001266796	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). 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 Laboratory Services, Illumina	RCV001109456	SCV001266797	uncertain significance	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 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 Laboratory Services, Illumina	RCV001109457	SCV001266798	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). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001241133	SCV001414128	likely benign	not provided	2025-01-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001241133	SCV004028123	uncertain significance	not provided	2023-08-14	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 in association with a MYO7A-related disorder to our knowledge; This variant is associated with the following publications: (PMID: 31847883)
CeGaT Center for Human Genetics Tuebingen	RCV001241133	SCV004131109	uncertain significance	not provided	2023-10-01	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004814944	SCV005070236	uncertain significance	Retinal dystrophy	2023-01-01	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001275891	SCV001461541	uncertain significance	Usher syndrome type 1B	2020-09-16	no assertion criteria provided	clinical testing