Submissions for variant NM_017433.5(MYO3A):c.1828A>G (p.Ile610Val)

gnomAD frequency: 0.00013  dbSNP: rs151254539

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000514971	SCV000609937	uncertain significance	not provided	2017-06-22	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000764888	SCV000896048	uncertain significance	Autosomal recessive nonsyndromic hearing loss 30	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000764888	SCV001261019	uncertain significance	Autosomal recessive nonsyndromic hearing loss 30	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.
GeneDx	RCV000514971	SCV001825383	uncertain significance	not provided	2021-09-20	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	RCV003343882	SCV004052138	uncertain significance	Inborn genetic diseases	2023-08-08	criteria provided, single submitter	clinical testing	The c.1828A>G (p.I610V) alteration is located in exon 18 (coding exon 16) of the MYO3A gene. This alteration results from a A to G substitution at nucleotide position 1828, causing the isoleucine (I) at amino acid position 610 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000514971	SCV004332201	uncertain significance	not provided	2025-01-08	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 610 of the MYO3A protein (p.Ile610Val). This variant is present in population databases (rs151254539, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with MYO3A-related conditions. ClinVar contains an entry for this variant (Variation ID: 445495). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt MYO3A protein function with a negative predictive value of 80%. 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.
Breakthrough Genomics, Breakthrough Genomics	RCV000514971	SCV005190683	uncertain significance	not provided		criteria provided, single submitter	not provided