Submissions for variant NM_015506.3(MMACHC):c.321G>A (p.Val107=)

gnomAD frequency: 0.43226  dbSNP: rs2275276

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000081738	SCV000113673	benign	not specified	2015-10-06	criteria provided, single submitter	clinical testing
GeneDx	RCV000081738	SCV000170316	benign	not specified	2013-05-29	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
PreventionGenetics, part of Exact Sciences	RCV000081738	SCV000312560	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000264092	SCV000357921	benign	Disorders of Intracellular Cobalamin Metabolism	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589848	SCV000699395	benign	not provided	2016-01-25	criteria provided, single submitter	clinical testing	Variant summary: The c.321G>A in MMACHC gene is a synonymous change that involves a non-conserved nucleotide. 3/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at an overall frequency of 47%, suggesting it is a common polymorphism. The variant has been reported as Benign by several reputable databases/clinical laboratories. Taken together, this variant has been classified as Benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001513687	SCV001721346	benign	Cobalamin C disease	2025-02-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001513687	SCV001750442	benign	Cobalamin C disease	2021-07-01	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000589848	SCV005284441	benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000081738	SCV001742517	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000081738	SCV001920516	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000081738	SCV001955967	benign	not specified		no assertion criteria provided	clinical testing