ClinVar Miner

Submissions for variant NM_015702.3(MMADHC):c.646C>G (p.Arg216Gly) (rs141093638)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186037 SCV000239001 uncertain significance not specified 2017-02-15 criteria provided, single submitter clinical testing The R216G variant in the MMADHC gene has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R216G variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R216G variant is a non-conservative amino acid substitution, which occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R216G as a variant of unknown significance. This variant has been observed to be maternally inherited.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000186037 SCV000708796 likely benign not specified 2017-05-30 criteria provided, single submitter clinical testing
Invitae RCV000641147 SCV000762769 likely benign Methylmalonic acidemia with homocystinuria cblD 2020-12-08 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV001091563 SCV001247688 likely benign not provided 2021-03-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001128816 SCV001288309 likely benign Disorders of Intracellular Cobalamin Metabolism 2018-01-12 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000641147 SCV001291096 uncertain significance Methylmalonic acidemia with homocystinuria cblD 2018-01-12 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.
Natera, Inc. RCV000641147 SCV001461405 benign Methylmalonic acidemia with homocystinuria cblD 2019-11-11 no assertion criteria provided clinical testing

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