Submissions for variant NM_005422.4(TECTA):c.4441A>G (p.Ser1481Gly)

gnomAD frequency: 0.00003  dbSNP: rs201946991

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000389890	SCV000368185	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.
Illumina Laboratory Services, Illumina	RCV000276827	SCV000368186	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000605514	SCV000712225	uncertain significance	not specified	2016-06-09	criteria provided, single submitter	clinical testing	The p.Ser1481Gly variant in TECTA has not been previously reported in individual s with hearing loss. This variant has been identified in 2/65888 of European chr omosomes and 1/10127 African chromosomes by the Exome Aggregation Consortium (Ex AC, http://exac.broadinstitute.org; dbSNP rs201946991). Although this variant ha s been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summar y, the clinical significance of the p.Ser1481Gly variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002520679	SCV002978436	uncertain significance	not provided	2024-11-12	criteria provided, single submitter	clinical testing	This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 1481 of the TECTA protein (p.Ser1481Gly). This variant is present in population databases (rs201946991, gnomAD 0.006%). This missense change has been observed in individual(s) with childhood deafness (PMID: 36597107). ClinVar contains an entry for this variant (Variation ID: 303026). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TECTA protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.