ClinVar Miner

Submissions for variant NM_004612.4(TGFBR1):c.52_54GCG[11] (p.Ala25_Ala26dup) (rs11466445)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000590468 SCV000698485 uncertain significance not provided 2017-03-30 criteria provided, single submitter clinical testing Variant summary: The TGFBR1 c.73_78dupGCGGCG (p.Ala25_Ala26dup) variant involves the duplication of six nucleotides in a repetitive region. One in silico tools predicts a deleterious outcome for this variant. The frequency of this variant in population databases is not available due to lack of coverage or very low coverage of the chromosomal region. This variant was reported to be found in 1/2436 control chromosomes in the literature at a frequency of 0.0004105, which is approximately 263 times the estimated maximal expected allele frequency of a pathogenic TGFBR1 variant (0.0000016), suggesting this variant is possibly a benign polymorphism, although the allele number is very low. This variant has been reported in a sporadic BrC patient without evidence of causality. The variant of interest has not, to our knowledge, been reported in affected individuals via reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as VUS-possibly benign until more evidence becomes available.
Invitae RCV000704697 SCV000833655 uncertain significance Thoracic aortic aneurysm and aortic dissection 2018-08-16 criteria provided, single submitter clinical testing This variant, c.73_78dupGCGGCG, results in the insertion of 2 amino acids to the TGFBR1 protein (p.Ala25_Ala26dup), but otherwise preserves the integrity of the reading frame. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with TGFBR1-related disease. ClinVar contains an entry for this variant (Variation ID: 496264). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acids is currently unknown. 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.

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