Submissions for variant NM_001048174.2(MUTYH):c.730C>T (p.Pro244Ser)

dbSNP: rs786201772

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000164236	SCV000214857	uncertain significance	Hereditary cancer-predisposing syndrome	2022-06-20	criteria provided, single submitter	clinical testing	The p.P272S variant (also known as c.814C>T), located in coding exon 10 of the MUTYH gene, results from a C to T substitution at nucleotide position 814. The proline at codon 272 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Counsyl	RCV000411809	SCV000487328	uncertain significance	Familial adenomatous polyposis 2	2015-12-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000411809	SCV000815040	uncertain significance	Familial adenomatous polyposis 2	2023-10-14	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 272 of the MUTYH protein (p.Pro272Ser). This variant is present in population databases (rs786201772, 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: 184896). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Human Genetics Bochum, Ruhr University Bochum	RCV002463653	SCV002758568	uncertain significance	Lynch syndrome 1	2022-10-24	criteria provided, single submitter	clinical testing	ACMG criteria used to clasify this variant: PM2, PP3
Human Genetics Bochum, Ruhr University Bochum	RCV000411809	SCV004042763	uncertain significance	Familial adenomatous polyposis 2	2022-10-21	criteria provided, single submitter	clinical testing	ACMG criteria used to clasify this variant: PM2_SUP_MOD, PP3
Baylor Genetics	RCV000411809	SCV004198799	uncertain significance	Familial adenomatous polyposis 2	2023-10-26	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000164236	SCV004358580	uncertain significance	Hereditary cancer-predisposing syndrome	2022-09-01	criteria provided, single submitter	clinical testing	This missense variant replaces proline with serine at codon 272 of the MUTYH protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250128 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
All of Us Research Program, National Institutes of Health	RCV000411809	SCV004843284	uncertain significance	Familial adenomatous polyposis 2	2023-06-28	criteria provided, single submitter	clinical testing	This missense variant replaces proline with serine at codon 272 of the MUTYH protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/250128 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.