Submissions for variant NM_005956.4(MTHFD1):c.878G>A (p.Arg293His)

gnomAD frequency: 0.00241  dbSNP: rs34181110

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000880050	SCV001023119	likely benign	not provided	2025-01-22	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV002054438	SCV002495850	uncertain significance	Combined immunodeficiency and megaloblastic anemia with or without hyperhomocysteinemia	2021-08-16	criteria provided, single submitter	clinical testing	MTHFD1 NM_005956.3 exon 10 p.Arg293His (c.878G>A): This variant has been reported in the literature in 1 individual in association with neural tube defects, segregating with disease in 1 affected family member (Hol 1998 PMID:9611072). This variant is present in 0.3% (217/68022) of European alleles and in 7 homozygotes in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/14-64425752-G-A?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID: 13632). This variant amino acid (Histidine) is present in several species including multiple mammals, and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Mendelics	RCV002247337	SCV002516606	benign	not specified	2022-05-04	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000880050	SCV004134321	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	MTHFD1: BP4
OMIM	RCV000014602	SCV000034856	risk factor	Spina bifida, folate-sensitive, susceptibility to	1998-02-01	no assertion criteria provided	literature only