ClinVar Miner

Submissions for variant NM_001128425.1(MUTYH):c.1163T>C (p.Leu388Pro) (rs1060501335)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000771347 SCV000903631 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-18 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586957 SCV000697667 likely pathogenic MUTYH-associated polyposis 2016-05-20 criteria provided, single submitter clinical testing Variant summary: The MUTYH c.1163T>C (p.Leu388Pro) variant involves the alteration of a conserved nucleotide and is located within the catalytic core of the glycosylase in MUTYH protein. 4/4 in silico tools predict a damaging outcome for this variant. This variant is absent in 119930 control chromosomes. This variant has been reported in two AFAP/FAP patients with another likely pathogenic variant in trans. Multiple functional studies showed that the variant leads to defective glycosylase activity. Taken together, this variant is classified as a Probable Disease Variant (or Likely Pathogenic) until more information becomes available.
Invitae RCV000465018 SCV000545761 pathogenic MYH-associated polyposis 2018-10-29 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 388 of the MUTYH protein (p.Leu388Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several individuals affected with adenomatous polyposis (PMID: 16134147, 16941501, 17949294). In two of these individuals, this variant has been observed on the opposite chromosome (in trans) from a pathogenic variant (PMID: 16134147, 16941501). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant is also known as c.1121 T>C, p.Leu374Pro, and p.L360P in the literature. Experimental studies have shown that this missense change severely impairs MUTYH DNA glycosylase activity (PMID: 25820570, 23322991, 20848659). For these reasons, this variant has been classified as Pathogenic.

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