Submissions for variant NM_005422.4(TECTA):c.3619G>A (p.Val1207Met)

gnomAD frequency: 0.00001  dbSNP: rs746231346

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000220819	SCV000272487	uncertain significance	not specified	2018-02-10	criteria provided, single submitter	clinical testing	he p.Val1207Met variant in TECTA has been identified by our laboratory in 1 indi vidual with hearing loss who did not carry any other variants in the TECTA gene. It has also been identified in 2/111716 European chromosomes by the Genome Aggr egation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs746231346). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools an d conservation analysis do not provide strong support for or against an impact t o the protein. In summary, the clinical significance of the p.Val1207Met variant is uncertain. ACMG/AMP Criteria applied: PM2.
Illumina Laboratory Services, Illumina	RCV001105580	SCV001262564	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	RCV001106726	SCV001263821	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.
Ambry Genetics	RCV003165547	SCV003876170	uncertain significance	Inborn genetic diseases	2023-03-06	criteria provided, single submitter	clinical testing	The c.3619G>A (p.V1207M) alteration is located in exon 11 (coding exon 11) of the TECTA gene. This alteration results from a G to A substitution at nucleotide position 3619, causing the valine (V) at amino acid position 1207 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.