ClinVar Miner

Submissions for variant NM_005422.4(TECTA):c.248C>T (p.Thr83Met)

gnomAD frequency: 0.00009  dbSNP: rs145898158
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Prof. Karen Avraham, Tel Aviv University RCV001004808 SCV001164297 pathogenic Autosomal recessive nonsyndromic hearing loss 21 2018-05-07 criteria provided, single submitter research Recessive, congenital, moderate-severe NSHL
GeneDx RCV001568737 SCV001792661 likely benign not provided 2021-04-28 criteria provided, single submitter clinical testing 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: 33111345, 18776598, 16718611, 30935366)
3billion RCV001004808 SCV002058224 uncertain significance Autosomal recessive nonsyndromic hearing loss 21 2022-01-03 criteria provided, single submitter clinical testing The variant was co-segregated with Deafness, autosomal recessive 21 in multiple affected family members with additional meioses meeting moderate evidence levels (PMID: 33111345, PP1_M). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000057, PM2_M). The variant has been reported to be in trans as homozygous in at least one similarly affected unrelated individual (PMID: 33111345, PM3_P). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.
Invitae RCV001568737 SCV004294981 pathogenic not provided 2022-11-28 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TECTA protein function. ClinVar contains an entry for this variant (Variation ID: 813831). This missense change has been observed in individual(s) with clinical features of autosomal recessive nonsyndromic deafness (PMID: 33111345; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs145898158, gnomAD 0.01%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 83 of the TECTA protein (p.Thr83Met).

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