Submissions for variant NM_001048174.2(MUTYH):c.128A>G (p.Gln43Arg)

gnomAD frequency: 0.00001  dbSNP: rs767237971

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000479870	SCV000569987	uncertain significance	not provided	2016-04-19	criteria provided, single submitter	clinical testing	This variant is denoted MUTYH c.212A>G at the cDNA level, p.Gln71Arg (Q71R) at the protein level, and results in the change of a Glutamine to an Arginine (CAG>CGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MUTYH Gln71Arg was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. MUTYH Gln71Arg occurs at a position that is not conserved and is not located in a known functional domain (Ruggieri 2013). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether MUTYH Gln71Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. Of note, MUTYH-Associated Polyposis (MAP) is a recessive condition associated with two pathogenic variants on opposite chromosomes in MUTYH.
Ambry Genetics	RCV001014554	SCV001175275	uncertain significance	Hereditary cancer-predisposing syndrome	2023-07-27	criteria provided, single submitter	clinical testing	The p.Q71R variant (also known as c.212A>G), located in coding exon 3 of the MUTYH gene, results from an A to G substitution at nucleotide position 212. The glutamine at codon 71 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001064252	SCV001229140	uncertain significance	Familial adenomatous polyposis 2	2024-05-22	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 71 of the MUTYH protein (p.Gln71Arg). This variant is present in population databases (rs767237971, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 420944). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Illumina Laboratory Services, Illumina	RCV001064252	SCV001257713	uncertain significance	Familial adenomatous polyposis 2	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.
Color Diagnostics, LLC DBA Color Health	RCV001014554	SCV001358828	uncertain significance	Hereditary cancer-predisposing syndrome	2019-02-07	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001064252	SCV004838109	uncertain significance	Familial adenomatous polyposis 2	2023-05-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001064252	SCV005056045	uncertain significance	Familial adenomatous polyposis 2	2024-02-19	criteria provided, single submitter	clinical testing