Submissions for variant NM_000260.4(MYO7A):c.4222C>G (p.Arg1408Gly)

gnomAD frequency: 0.00003  dbSNP: rs377391891

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155235	SCV000204921	uncertain significance	not specified	2013-11-22	criteria provided, single submitter	clinical testing	The Arg1408Gly variant in MYO7A has not been previously reported in individuals with hearing loss, but has been identified in 0.02% (2/8364) of European America n chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.ed u; dbSNP rs377391891). Computational analyses (biochemical amino acid properties , conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that this may impact the protein, though this information is not predictive enough to determine pathogen icity. In summary, additional data is needed to fully assess the clinical signif icance of this variant.
Invitae	RCV001051946	SCV001216131	uncertain significance	not provided	2022-08-08	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1408 of the MYO7A protein (p.Arg1408Gly). This variant is present in population databases (rs377391891, gnomAD 0.004%). 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: 178487). 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 not 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.
Ambry Genetics	RCV002516124	SCV003735110	uncertain significance	Inborn genetic diseases	2022-11-10	criteria provided, single submitter	clinical testing	The c.4222C>G (p.R1408G) alteration is located in exon 32 (coding exon 31) of the MYO7A gene. This alteration results from a C to G substitution at nucleotide position 4222, causing the arginine (R) at amino acid position 1408 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV001051946	SCV003761593	uncertain significance	not provided	2023-01-24	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
CeGaT Center for Human Genetics Tuebingen	RCV001051946	SCV004131124	uncertain significance	not provided	2024-01-01	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001831963	SCV002088440	uncertain significance	Usher syndrome type 1B	2019-11-11	no assertion criteria provided	clinical testing