ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.1057G>T (p.Gly353Trp) (rs587778539)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000198794 SCV000254699 uncertain significance MYH-associated polyposis 2020-10-03 criteria provided, single submitter clinical testing This sequence change replaces glycine with tryptophan at codon 381 of the MUTYH protein (p.Gly381Trp). The glycine residue is moderately conserved and there is a large physicochemical difference between glycine and tryptophan. This variant is present in population databases (rs587778539, ExAC 0.009%). This sequence change has been reported in the heterozygous state in an individual affected with attenuated adenomatous polyposis coli (Leiden Open Variation Database, PMID: 21520333). However, the affected individual was found to also carry a pathogenic APC variant that could explain their reported condition. ClinVar contains an entry for this variant (Variation ID: 134863). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly 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.
Color Health, Inc RCV000580244 SCV000685543 uncertain significance Hereditary cancer-predisposing syndrome 2020-08-19 criteria provided, single submitter clinical testing This missense variant replaces glycine with tryptophan at codon 381 of the MUTYH protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 2/250112 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.
Mendelics RCV000198794 SCV000837755 uncertain significance MYH-associated polyposis 2018-07-02 criteria provided, single submitter clinical testing
ITMI RCV000121596 SCV000085792 not provided not specified 2013-09-19 no assertion provided reference population

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