ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.848A>C (p.Tyr283Ser)

dbSNP: rs201931669
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001058018 SCV001222553 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-07-29 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 283 of the MLH1 protein (p.Tyr283Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MLH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 853241). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MLH1 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.
Ambry Genetics RCV002445303 SCV002681606 uncertain significance Hereditary cancer-predisposing syndrome 2021-05-24 criteria provided, single submitter clinical testing The p.Y283S variant (also known as c.848A>C), located in coding exon 10 of the MLH1 gene, results from an A to C substitution at nucleotide position 848. The tyrosine at codon 283 is replaced by serine, an amino acid with dissimilar 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.

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