ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.548G>A (p.Gly183Asp) (rs587781864)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130180 SCV000185017 pathogenic Hereditary cancer-predisposing syndrome 2018-09-29 criteria provided, single submitter clinical testing The p.G183D pathogenic mutation (also known as c.548G>A), located in coding exon 7 of the MUTYH gene, results from a G to A substitution at nucleotide position 548. The glycine at codon 183 is replaced by aspartic acid, an amino acid with similar properties. This alteration has been reported in conjunction with another pathogenic MUTYH mutation in two brothers with polypopsis (Skrzypczak M et al. Hered. Cancer Clin. Pract. 2006;4:43-7). In addition, this alteration has been identified in several individuals with a second known MUTYH mutation in trans and a personal and family history consistent with MUTYH-associated poypopsis (MAP) (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Invitae RCV000456187 SCV000545737 uncertain significance MYH-associated polyposis 2020-11-01 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 183 of the MUTYH protein (p.Gly183Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is present in population databases (rs587781864, ExAC 0.02%). This variant has been reported in two siblings affected with familial adenomatous polyposis (FAP) (PMID: 20223003). In this family the variant co-occurs with a second pathogenic variant in MUTYH. This variant also has been observed in trans with a second pathogenic MUTYH variant in an individual with colon cancer (Invitae). It is also known as 506G>A (G169D) in the literature. ClinVar contains an entry for this variant (Variation ID: 141595). 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: Tolerated; PolyPhen-2: Probably Damaging; 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.
GeneDx RCV000519177 SCV000619213 likely pathogenic not provided 2020-10-15 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as c.506G>A, p.Gly169Asp; This variant is associated with the following publications: (PMID: 20223003)
Color Health, Inc RCV000130180 SCV000690583 likely pathogenic Hereditary cancer-predisposing syndrome 2019-12-05 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000519177 SCV001470577 uncertain significance not provided 2020-07-28 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000519177 SCV000592687 uncertain significance not provided no assertion criteria provided clinical testing The MUTYH p.Gly183Asp variant was identified in literature in 1 out of 90 Polish patients with familial polyposis and negative for an APC mutation (Skrzypczak 2006). In this reported case, the p.Tyr179Cys was also identified on the other allele; however, the pathogenicity of the p.Gly183Asp variant could not be determined with certainty. This variant was not reported in the HGMD, COSMIC, InSiGHT or LOVD databases. The p.Gly183 residue is conserved in mammals but not in Fission yeast; and computational analyses (PolyPhen2, SIFT, AlignGVGD) provide inconsistent predictions regarding the impact to the protein. This variant is not predicted to affect normal splicing. In summary, based on the above information the clinical significance of this variant cannot be determined at this time. Therefore, this variant is classified as a variant of unknown significance.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.