Submissions for variant NM_005422.4(TECTA):c.4813G>A (p.Val1605Ile)

gnomAD frequency: 0.00014  dbSNP: rs201952240

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000221507	SCV000270909	benign	not specified	2017-07-05	criteria provided, single submitter	clinical testing	p.Val1605Ile in exon 14 of TECTA: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. Of note, 3 mammals have an isoleucine (Ile) at this position despite high nearby a mino acid conservation. In addition, computational prediction tools do not sugge st a high likelihood of impact to the protein. It has been identified in 0.6% (5 8/10152) of Ashkenazi Jewish chromosomes by the genome Aggregation Database (gno mAD, http://gnomad.broadinstitute.org; dbSNP rs201952240).
Illumina Laboratory Services, Illumina	RCV001103826	SCV001260639	uncertain significance	Autosomal recessive nonsyndromic hearing loss 21	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV001103827	SCV001260640	uncertain significance	Autosomal dominant nonsyndromic hearing loss 12	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003736648	SCV004549349	benign	not provided	2022-12-08	criteria provided, single submitter	clinical testing
GeneDx	RCV003736648	SCV005325491	uncertain significance	not provided	2023-11-14	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Located in the von Willebrand factor type D region of the zonadhesin domain (PMID: 21520338); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 21520338, 31554319, 9590290, 22980975)
PreventionGenetics, part of Exact Sciences	RCV003947714	SCV004758528	likely benign	TECTA-related disorder	2020-07-27	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).