ClinVar Miner

Submissions for variant NM_002454.3(MTRR):c.1677-2dup

gnomAD frequency: 0.00009  dbSNP: rs747255318
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000806246 SCV000946233 uncertain significance Methylcobalamin deficiency type cblE 2024-01-22 criteria provided, single submitter clinical testing This sequence change falls in intron 12 of the MTRR gene. It does not directly change the encoded amino acid sequence of the MTRR protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs747255318, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with MTRR-related conditions. ClinVar contains an entry for this variant (Variation ID: 650985). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
GeneDx RCV003128710 SCV003805450 uncertain significance not provided 2023-02-17 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
PreventionGenetics, part of Exact Sciences RCV003965598 SCV004782233 likely benign MTRR-related disorder 2020-04-02 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Natera, Inc. RCV000806246 SCV001459131 uncertain significance Methylcobalamin deficiency type cblE 2020-01-24 no assertion criteria provided clinical testing

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