Submissions for variant NM_144672.4(OTOA):c.746_751delinsA (p.Ser249fs)

dbSNP: rs876657716

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000222173	SCV000271427	pathogenic	Rare genetic deafness	2015-07-01	criteria provided, single submitter	clinical testing	The p.Ser249fs variant in OTOA has not been previously reported in individuals w ith hearing loss. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 249 and leads to a prema ture termination codon 21 amino acids downstream. This alteration is then predic ted to lead to a truncated or absent protein. Loss of function of the OTOA gene is an established disease mechanism in autosomal recessive sensorineural hearing loss. In summary, this variant meets our criteria to be classified as pathogeni c for hearing loss in an autosomal recessive manner (www.partners.org/personaliz edmedicine/lmm), based on the predicted impact of the variant.
GeneDx	RCV001008498	SCV001168269	likely pathogenic	not provided	2023-04-03	criteria provided, single submitter	clinical testing	Frameshift 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 (gnomAD); Has not been previously published as pathogenic or benign to our knowledge