ClinVar Miner

Submissions for variant NM_005334.3(HCFC1):c.218C>T (p.Ala73Val) (rs397515486)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224484 SCV000281353 pathogenic not provided 2015-12-23 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Strasbourg University Hospital RCV000224133 SCV000281741 pathogenic Intellectual disability 2014-07-25 criteria provided, single submitter clinical testing present in the affected brother
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001199845 SCV001370569 pathogenic Cobalamin C disease 2020-05-12 criteria provided, single submitter clinical testing Variant summary: HCFC1 c.218C>T (p.Ala73Val) results in a non-conservative amino acid change located in the the first kelch domain (Yu_2013) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 161726 control chromosomes (gnomAD). c.218C>T has been reported in the literature in individuals affected with Methylmalonic Acidemia With Homocystinuria as well as one individual whose parents were negative for the mutation, suggesting that it arose de novo (Yu_2013, Redin_2014). Functional studies report this variant results in reducing the level of MMACHC expression and in biochemical abnormalities (Yu_2013, Quintana_2014). One ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000057507 SCV000088619 pathogenic Mental retardation 3, X-linked 2013-09-05 no assertion criteria provided literature only

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