ClinVar Miner

Submissions for variant NM_000255.4(MMUT):c.567T>G (p.Asn189Lys) (rs1561959114)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757496 SCV000885745 likely pathogenic not provided 2018-06-19 criteria provided, single submitter clinical testing The MUT c.567T>G; p.Asn189Lys variant has been described in the compound heterozygous state in individuals with methylmalonic aciduria (Han 2015, Jung 2004, Worgan 2006). It is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The asparagine at codon 189 is highly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. Additionally, another variant at this codon (c.566A>T; p.Asn189Ile) has been reported in at least one individual with methylmalonic aciduria and is considered pathogenic (Forny 2016). Based on available information, this variant is considered likely pathogenic. Pathogenic MUT variants are inherited in an autosomal recessive manner and are associated with methylmalonic aciduria, mut(0) type (MIM: 251000). References: Forny P et al. Molecular Genetic Characterization of 151 Mut-Type Methylmalonic Aciduria Patients and Identification of 41 Novel Mutations in MUT. Hum Mutat. 2016 Aug;37(8):745-54. Han LS et al. Clinical features and MUT gene mutation spectrum in Chinese patients with isolated methylmalonic acidemia: identification of ten novel allelic variants. World J Pediatr. 2015 Nov;11(4):358-65. Jung JW et al. Mutation analysis of the MCM gene in Korean patients with MMA. Mol Genet Metab. 2005 Apr;84(4):367-70. Epub 2004 Dec 19. Worgan LC et al. Spectrum of mutations in mut methylmalonic acidemia and identification of a common Hispanic mutation and haplotype. Hum Mutat. 2006 Jan;27(1):31-43.

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