ClinVar Miner

Submissions for variant NM_000546.5(TP53):c.375+5_375+11del (rs730882021)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000161062 SCV000211794 uncertain significance not provided 2014-04-07 criteria provided, single submitter clinical testing This variant is denoted TP53 c.375+(5_11)delGTTGCCC or IVS4+(5_11)delGTTGCCC and consists of a deletion of seven consecutive nucleotides starting at the +5 position of intron 4 of the TP53 gene. The normal sequence, with the bases that are deleted in brackets, is GTCA[delGTTGCCC]TGAG. Multiple in silico models predict this variant destroys the nearby natural donor site, possibly leading to abnormal gene splicing. TP53 c.375+(5_11)delGTTGCCC has not, to our knowledge, been published in the literature as pathogenic or benign. This variant was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Based on currently available information, it is unclear whether TP53 c.375+(5_11)delGTTGCCC is pathogenic or benign. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000780781 SCV000918323 uncertain significance not specified 2017-09-15 criteria provided, single submitter clinical testing Variant summary: The TP53 c.375+5_375+11delGTTGCCC variant involves the deletion of seven intronic nucleotides. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict that this variant may weaken or eliminate the normal splicing 5' donor site. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 245208 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.

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