Submissions for variant NM_016239.4(MYO15A):c.3311dup (p.Gly1104_Glu1105insTer)

dbSNP: rs794729637

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001657964	SCV001874740	pathogenic	not provided	2021-08-03	criteria provided, single submitter	clinical testing	Observed on the same allele (in cis) as another variant in the MYO15A gene in a patient with hearing loss in published literature (Sheppard et al., 2018); this variant in cis has been classified as benign at GeneDx; Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 26969326, 29907799)
Athena Diagnostics	RCV001657964	SCV001880559	pathogenic	not provided	2021-02-25	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001657964	SCV004298132	pathogenic	not provided	2023-10-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu1105*) in the MYO15A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO15A are known to be pathogenic (PMID: 17546645). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with deafness (PMID: 26969326, 29907799). ClinVar contains an entry for this variant (Variation ID: 203363). For these reasons, this variant has been classified as Pathogenic.
Division of Human Genetics, Children's Hospital of Philadelphia	RCV000185530	SCV000238405	pathogenic	Autosomal recessive nonsyndromic hearing loss 3	2014-06-23	no assertion criteria provided	research	The variant (c.3311dupG;p.E1105*) is a frameshift variant at amino acid position 1105 predicted to result in a truncated protein. It has not been reported, but another variant resulting in the same amino acid change, c.3313G>T;p.E1105*, has been reported in a patient with hearing loss (Nal et al. 2007, PMID: 17546645).