ClinVar Miner

Submissions for variant NM_001048171.1(MUTYH):c.958C>A (p.Pro320Thr) (rs587778537)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000218057 SCV000276032 uncertain significance Hereditary cancer-predisposing syndrome 2020-04-09 criteria provided, single submitter clinical testing The p.P334T variant (also known as c.1000C>A), located in coding exon 12 of the MUTYH gene, results from a C to A substitution at nucleotide position 1000. The proline at codon 334 is replaced by threonine, 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.
Counsyl RCV000411238 SCV000487382 uncertain significance MYH-associated polyposis 2016-10-13 criteria provided, single submitter clinical testing
Invitae RCV000411238 SCV000545796 uncertain significance MYH-associated polyposis 2020-10-07 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 334 of the MUTYH protein (p.Pro334Thr). The proline residue is weakly conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs587778537, ExAC 0.02%) but has not been reported in the literature in individuals with a MUTYH-related disease. ClinVar contains an entry for this variant (Variation ID: 134861). General algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD), and an algorithm developed specifically for the MUTYH gene (PMID: 23621914), suggest that this missense change is likely to be tolerated. However, these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Health, Inc RCV000218057 SCV000903810 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-29 criteria provided, single submitter clinical testing
ITMI RCV000121594 SCV000085790 not provided not specified 2013-09-19 no assertion provided reference population
GeneDx RCV001576763 SCV001804015 uncertain significance not provided 2021-04-05 no assertion criteria provided clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Identified in healthy individuals undergoing whole genome sequencing (Bodian 2014); This variant is associated with the following publications: (PMID: 24470512, 24728327)

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