ClinVar Miner

Submissions for variant NM_000255.4(MMUT):c.1956+2T>C

dbSNP: rs750619189
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000664805 SCV000788820 likely pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2017-01-06 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000664805 SCV000893720 pathogenic Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2018-10-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000664805 SCV000916150 uncertain significance Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency 2018-11-06 criteria provided, single submitter clinical testing This variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. It was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene and cDNA change. No publications were found based on this search. Due to the potential impact of splice donor variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for this disease.
Invitae RCV001376546 SCV001236194 likely pathogenic not provided 2023-12-31 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 11 of the MUT gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MUT are known to be pathogenic (PMID: 15781192). This variant is present in population databases (rs750619189, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with MUT-related conditions. ClinVar contains an entry for this variant (Variation ID: 550143). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Natera, Inc. RCV001276632 SCV001463084 likely pathogenic Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency 2020-09-16 no assertion criteria provided clinical testing

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