Submissions for variant NM_152269.5(MTRFR):c.413A>G (p.Lys138Arg)

gnomAD frequency: 0.00078  dbSNP: rs147328685

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124049	SCV000167458	benign	not specified	2014-04-09	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.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	RCV000124049	SCV000257829	uncertain significance	not specified	2015-05-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000513336	SCV000608668	uncertain significance	not provided	2022-11-01	criteria provided, single submitter	clinical testing	MTRFR: PM2:Supporting, BP4
Invitae	RCV001081513	SCV001002940	likely benign	Combined oxidative phosphorylation defect type 7; Spastic paraplegia	2024-01-22	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001113859	SCV001271668	uncertain significance	Combined oxidative phosphorylation defect type 7	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, this variant 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, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847744	SCV002106300	likely benign	Hereditary spastic paraplegia	2019-12-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003965041	SCV004778968	likely benign	MTRFR-related condition	2022-03-30	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).