Submissions for variant NM_001080467.3(MYO5B):c.946G>A (p.Gly316Arg)

gnomAD frequency: 0.00003  dbSNP: rs753558336

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000289007	SCV000409026	uncertain significance	Congenital microvillous atrophy	2017-04-27	criteria provided, single submitter	clinical testing	The MYO5B c.946G>A (p.Gly316Arg) variant has been reported in a single study in which it was found in a homozygous state in one individual diagnosed with diarrhea with microvillus atrophy (Szperl et al. 2011). The variant was absent from 50 ethnically matched control individuals and is reported at a frequency of 0.00095 in the Latino population of the Exome Aggregation Consortium. The variant results in a substitution of a small aliphatic residue with a large charged arginine and affects residues localized in critical regions of the motor domain which is important for allosteric rearrangements (van der Velde et al. 2013). The evidence for this variant is limited. The p.Gly316Arg variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for diarrhea with microvillus atrophy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Revvity Omics, Revvity	RCV003137929	SCV003817829	uncertain significance	not provided	2021-08-30	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003418034	SCV004113097	uncertain significance	MYO5B-related disorder	2022-11-18	criteria provided, single submitter	clinical testing	The MYO5B c.946G>A variant is predicted to result in the amino acid substitution p.Gly316Arg. This variant was reported in the homozygous state in an individual with microvillus inclusion disease and in an individual with IPEX (Immune dysregulation, polyendocrinopathy, enteropathy, X-linked)-like syndrome (Szperl et al 2011. PubMed ID: 21206382; Baxter SK et al 2021. PubMed ID: 33864888). This variant is reported in 0.037% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/18-47511088-C-T). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000289007	SCV004805027	pathogenic	Congenital microvillous atrophy	2024-03-17	criteria provided, single submitter	research
GeneDx	RCV003137929	SCV005080219	uncertain significance	not provided	2023-12-07	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25525159, 21206382, 24014347, 33864888)