Submissions for variant NM_005422.4(TECTA):c.3406G>C (p.Asp1136His)

gnomAD frequency: 0.00031  dbSNP: rs147890616

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000151978	SCV000200528	uncertain significance	not specified	2013-04-06	criteria provided, single submitter	clinical testing	The Asp1136His variant in TECTA has been reported in a Spanish family with domin ant postlingual mid-frequency hearing loss (Hildebrand 2011); however, the autho rs did not report the number of family members who were tested and whether the v ariant co-segregated in all affected members. This variant has also been identif ied in 0.05% (2/4406) of African American chromosomes by the NHLBI Exome Sequenc ing Project and in 1/100 (1%) Puerto Rican chromosomes by the 1000 Genomes Proje ct (http://evs.gs.washington.edu/EVS/; dbSNP rs147890616). Although, this varian t has been reported in the general population, its frequency is not high enough to rule out a pathogenic role. Computational analyses (biochemical amino acid pr operties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong su pport for or against an impact to the protein. In summary, additional informatio n is needed to fully assess the clinical significance of this variant.
Eurofins Ntd Llc (ga)	RCV000726310	SCV000343651	uncertain significance	not provided	2016-08-17	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000763711	SCV000894591	uncertain significance	Autosomal dominant nonsyndromic hearing loss 12; Autosomal recessive nonsyndromic hearing loss 21	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001103636	SCV001260427	uncertain significance	Autosomal recessive nonsyndromic hearing loss 21	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001103637	SCV001260428	uncertain significance	Autosomal dominant nonsyndromic hearing loss 12	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx	RCV000726310	SCV001789164	uncertain significance	not provided	2024-06-11	criteria provided, single submitter	clinical testing	Reported in association with autosomal dominant hearing loss in published literature (PMID: 21520338); In silico analysis indicates that this missense variant does not alter protein structure/function; Located in the von Willebrand factor type D3 subdomain of the zonadhesin domain (PMID: 21520338, 31554319, 9590290); This variant is associated with the following publications: (PMID: 25262649, 30245029, 27368438, 21520338, 31554319, 9590290)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000726310	SCV002165013	benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000726310	SCV001960141	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000726310	SCV001974790	uncertain significance	not provided		no assertion criteria provided	clinical testing