Submissions for variant NM_004999.4(MYO6):c.92T>C (p.Ile31Thr)

gnomAD frequency: 0.00093  dbSNP: rs148735953

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000825199	SCV000966476	likely benign	not specified	2012-04-30	criteria provided, single submitter	clinical testing	Ile31Thr in Exon 02 of MYO6: This variant is not expected to have clinical signi ficance because it has been identified in 0.4% (14/3738) of African American chr omosomes from a broad population by the NHLBI Exome Sequencing Project (http://e vs.gs.washington.edu/EVS; dbSNP rs148735953).
GeneDx	RCV001355675	SCV001819537	likely benign	not provided	2021-05-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001355675	SCV002362342	likely benign	not provided	2024-12-23	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355675	SCV001550626	uncertain significance	not provided		no assertion criteria provided	clinical testing	The MYO6 p.I31T variant was not identified in the literature but was identified in dbSNP (ID: rs148735953) and ClinVar (classified as likely benign by Laboratory for Molecular Medicine). The variant was identified in control databases in 81 of 282852 chromosomes at a frequency of 0.0002864, and was observed at the highest frequency in the African population in 77 of 24968 chromosomes (freq: 0.003084) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.I31 residue is conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV004756044	SCV005359274	likely benign	MYO6-related disorder	2024-03-18	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).