Submissions for variant NM_005422.4(TECTA):c.5488G>A (p.Val1830Met)

gnomAD frequency: 0.00011  dbSNP: rs189181502

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Testing Center for Deafness, Department of Otolaryngology Head & Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital	RCV001002756	SCV000992398	likely benign	Autosomal dominant nonsyndromic hearing loss 12		criteria provided, single submitter	case-control
GeneDx	RCV001664484	SCV001872922	uncertain significance	not provided	2021-08-03	criteria provided, single submitter	clinical testing	Identified in a patient with hearing loss in published literature who also harbored a variant in the POU4F3 gene which the authors considered to be causative; the TECTA variant was observed in unaffected family members (He et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21520338, 31554319, 9590290, 16718611, 28053790)
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV004789235	SCV005399205	likely benign	Nonsyndromic genetic hearing loss	2020-10-19	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 2-Likely benign. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. However, dominant negative has been suggested as a mechanism of disease for missense variants in this gene (OMIM). (N) 0108 - This gene is known to be associated with both recessive and dominant disease. This gene is associated with autosomal dominant and recessive deafness (OMIM). (N) 0200 - Variant is predicted to result in a missense amino acid change from valine to methionine (exon 17). (N) 0251 - Variant is heterozygous. (N) 0302 - Variant is present in gnomAD <0.001 for a dominant condition (v2: 104 Heterozygotes, 1 Homozygote). (P) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2: 1 Heterozygotes, 0 Homozygote). (N) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (N) 0600 - Variant is located in an annotated domain or motif. This variant is in the Zona pellucida domain (NCBI conserved domain). (N) 0705 - No comparable variants have previous evidence for pathogenicity. (N) 0806 - Moderate previous evidence of neutrality in unrelated individuals. This variant was reported in one individual with autosomal dominant nonsyndromic hearing loss but did not segregate with other affected family members (PMID: 28053790). (B) 1007 - No published functional evidence has been identified for this variant. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign
CeGaT Center for Human Genetics Tuebingen	RCV001664484	SCV005433814	uncertain significance	not provided	2024-11-01	criteria provided, single submitter	clinical testing	TECTA: PM2
Labcorp Genetics (formerly Invitae), Labcorp	RCV001664484	SCV005774283	likely benign	not provided	2025-01-20	criteria provided, single submitter	clinical testing