Submissions for variant NM_015506.3(MMACHC):c.328_331del (p.Asn110fs)

dbSNP: rs796052000

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000186035	SCV000238999	pathogenic	not provided	2020-08-21	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 24126030, 23954310, 16311595, 19370762, 30157807)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000531346	SCV000640287	pathogenic	Cobalamin C disease	2025-01-01	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asn110Aspfs*13) in the MMACHC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MMACHC are known to be pathogenic (PMID: 16311595). This variant is present in population databases (rs777767443, gnomAD 0.04%). This premature translational stop signal has been observed in individuals with methylmalonic aciduria and homocystinuria, cobalamin C (cblC) type (PMID: 16311595, 19370762, 23954310, 24126030). ClinVar contains an entry for this variant (Variation ID: 203835). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000531346	SCV000699396	pathogenic	Cobalamin C disease	2016-04-12	criteria provided, single submitter	clinical testing	Variant summary: The c.328_331delAACC variant results in a premature termination codon, predicted to cause a truncated or absent MMACHC protein, which is a commonly known mechanism for disease. Truncations downstream of this position have also been associated with CBLC phenotype (e.g. p.Arg132X). One in-silico tool predicts damaging outcome for this variant. This variant is not found in approximately120716 control chromosomes from the large and broad populations of ExAC. This variant has been reported in several patients with CBLC. Multiple reputable databases and one clinical lab has classified this variant as pathogenic. Taken together, this variant has been classified as a Disease Variant/Pathogenic.
Baylor Genetics	RCV000531346	SCV001162898	pathogenic	Cobalamin C disease	2024-02-23	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000531346	SCV002017509	pathogenic	Cobalamin C disease	2021-02-09	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000531346	SCV002811620	pathogenic	Cobalamin C disease	2021-12-02	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000531346	SCV004178152	pathogenic	Cobalamin C disease	2023-04-11	criteria provided, single submitter	clinical testing
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000531346	SCV005441860	pathogenic	Cobalamin C disease	2024-12-19	criteria provided, single submitter	clinical testing
Counsyl	RCV000531346	SCV001132249	pathogenic	Cobalamin C disease	2017-03-16	no assertion criteria provided	clinical testing
Natera, Inc.	RCV001273219	SCV001456011	pathogenic	Methylmalonic acidemia with homocystinuria cblC	2020-09-16	no assertion criteria provided	clinical testing