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

dbSNP: rs750619189

Total submissions: 5

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
Labcorp Genetics (formerly Invitae), Labcorp	RCV001376546	SCV001236194	pathogenic	not provided	2025-01-15	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%). Disruption of this splice site has been observed in individual(s) with methylmalonic acidemia (PMID: 16281286). 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. For these reasons, this variant has been classified as Pathogenic.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000664805	SCV004809648	likely pathogenic	Methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency	2024-04-04	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001276632	SCV001463084	likely pathogenic	Methylmalonic aciduria due to complete methylmalonyl-CoA mutase deficiency	2020-09-16	no assertion criteria provided	clinical testing