ClinVar Miner

Submissions for variant NM_147196.3(TMIE):c.34G>T (p.Val12Leu)

gnomAD frequency: 0.00014  dbSNP: rs397517867
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000041231 SCV000064922 uncertain significance not specified 2015-09-08 criteria provided, single submitter clinical testing The p.Val12Leu variant in TMIE has now been identified by our laboratory in the heterozygous state in 2 individuals with hearing loss; however, a variant affect ing the other copy of the TMIE gene has not been identified in either of them. D ata from large population studies are insufficient to assess the frequency of th is variant in the general population. Computational prediction tools and conserv ation analysis suggest that the p.Val12Leu variant may not impact the protein, t hough this information is not predictive enough to rule out pathogenicity. In su mmary, the clinical significance of the p.Val12Leu variant is uncertain.
Illumina Laboratory Services, Illumina RCV000400167 SCV000444720 uncertain significance Autosomal recessive nonsyndromic hearing loss 6 2018-01-12 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 RCV001852836 SCV002121434 uncertain significance not provided 2022-08-09 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 12 of the TMIE protein (p.Val12Leu). This variant is present in population databases (rs397517867, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TMIE-related conditions. ClinVar contains an entry for this variant (Variation ID: 47959). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV002513576 SCV003707835 uncertain significance Inborn genetic diseases 2022-10-27 criteria provided, single submitter clinical testing The c.34G>T (p.V12L) alteration is located in exon 1 (coding exon 1) of the TMIE gene. This alteration results from a G to T substitution at nucleotide position 34, causing the valine (V) at amino acid position 12 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV001852836 SCV005078620 uncertain significance not provided 2024-05-29 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Breakthrough Genomics, Breakthrough Genomics RCV001852836 SCV005190081 uncertain significance not provided criteria provided, single submitter not provided

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