Submissions for variant NM_005422.4(TECTA):c.4633G>A (p.Val1545Ile)

gnomAD frequency: 0.00024  dbSNP: rs377156351

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038498	SCV000062176	uncertain significance	not specified	2013-02-05	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The 4633G>A Val1545 Ile variant in TECTA has not been previously identified by our laboratory but ha s been seen in 0.02% (2/8598) of European American chromosomes by the NHLBI Exom e Sequencing Project (http://evs.gs.washington.edu/EVS). Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT ) do not provide strong support for or against an impact to the protein, though one mammal, Pika, carries the same variant in its normal sequence, suggesting a less likely impact to protein function. It should be noted that both recessive a nd dominant mutations have been described for TECTA, with recessive variants pri marily loss of function and dominant typically missense variants. Although the c linical significance of this variant is unknown, we would lean towards a more li kely benign role given the lack of amino acid conservation across all mammals.
Baylor Genetics	RCV001336816	SCV001530313	uncertain significance	Autosomal dominant nonsyndromic hearing loss 12	2018-06-25	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx	RCV001659974	SCV001872787	uncertain significance	not provided	2023-10-06	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31554319, 9590290, 21520338)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001659974	SCV002217572	likely benign	not provided	2024-12-07	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001659974	SCV004129511	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	TECTA: BP4
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001659974	SCV001956127	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001659974	SCV001970785	likely benign	not provided		no assertion criteria provided	clinical testing