ClinVar Miner

Submissions for variant NM_007332.3(TRPA1):c.2294C>T (p.Thr765Met)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV004071202 SCV003526582 uncertain significance not specified 2022-11-21 criteria provided, single submitter clinical testing The c.2294C>T (p.T765M) alteration is located in exon 19 (coding exon 19) of the TRPA1 gene. This alteration results from a C to T substitution at nucleotide position 2294, causing the threonine (T) at amino acid position 765 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen RCV004721127 SCV005329909 likely benign not provided 2024-08-01 criteria provided, single submitter clinical testing TRPA1: BP4, BS1
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004071202 SCV005725555 uncertain significance not specified 2024-11-27 criteria provided, single submitter clinical testing Variant summary: TRPA1 c.2294C>T (p.Thr765Met) results in a non-conservative amino acid change located in the Ion transport domain (IPR005821) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. Several computational tools predict a significant impact on normal splicing: Two predict the variant weakens a 5' donor site. One predicts the variant has no significant impact on splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00014 in 249124 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in TRPA1 causing Familial episodic pain syndrome with predominantly upper body involvement, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.2294C>T in individuals affected with Familial episodic pain syndrome with predominantly upper body involvement and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2205866). Based on the evidence outlined above, the variant was classified as uncertain significance.

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