ClinVar Miner

Submissions for variant NM_000108.5(DLD):c.788G>A (p.Arg263His) (rs145670503)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000676803 SCV000238807 uncertain significance not provided 2018-08-14 criteria provided, single submitter clinical testing The R263H missense substitution has not been published as a mutation. This variant has been reported in dbSNP as a polymorphism (rs145670503); however, the NHLBI ESP Exome Variant Server reports R263H was observed in only 10/5,000 individuals. The amino acid change is conservative as both Arginine and Histidine are positively charged amino acids. This change occurs at a position in the DLD protein that is conserved in mammals. In-silico analyses are not consistent in their predictions of whether R263H is damaging to the DLD protein. Therefore, based on the currently available information, it is unclear whether R263H is a disease-causing mutation or a rare benign variant.
Invitae RCV000653827 SCV000775717 uncertain significance Maple syrup urine disease, type 3 2019-09-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 263 of the DLD protein (p.Arg263His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs145670503, ExAC 0.2%). This variant has not been reported in the literature in individuals with DLD-related disease. ClinVar contains an entry for this variant (Variation ID: 203681). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000653827 SCV000895813 uncertain significance Maple syrup urine disease, type 3 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001161965 SCV001323887 uncertain significance Leigh syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001161966 SCV001323888 uncertain significance Pyruvate dehydrogenase complex deficiency 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV000653827 SCV001323889 uncertain significance Maple syrup urine disease, type 3 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000676803 SCV000802611 uncertain significance not provided 2016-02-24 no assertion criteria provided clinical testing

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