ClinVar Miner

Submissions for variant NM_021930.6(RINT1):c.1671_1671+2del (rs869312981)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000210515 SCV000266765 uncertain significance Cowden syndrome 2015-10-23 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 11 of the RINT1 mRNA (c.1671_1671+2delTGT), corresponding to the last nucleotide of exon 11 and the donor splice site in intron 11. This variant is present in population databases (ExAC, 0.01%) but has not been reported in the literature. Nucleotide substitutions at the last nucleotide of the exon and donor splice site in the intron are relatively common causes of aberrant splicing (PMID: 17576681), but according to multiple splice site algorithms this particular variant does not result in a significant splicing alteration. An adjacent GT dinucleotide (c.1669_1670) has the potential to serve as a new donor splice site that, if used, would result in an in-frame deletion of Val557. There is also the possibility that this alternate site is not used, which may result in aberrant splicing. Neither of these predictions has been confirmed by published functional studies. In summary, this is a rare variant that deletes nucleotides that may affect the amino acid sequence or splicing of RINT1, but the impact of these predicted changes on protein function is not known. In addition, although loss-of-function variants in RINT1 have been observed in families with breast cancer (PMID: 25050558), the currently available evidence is insufficient to establish a causal relationship between variants in RINT1 and breast cancer. Therefore, this change has been classified as a Variant of Uncertain Significance.

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