ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.2024G>A (p.Ser675Asn) (rs781637991)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000221266 SCV000279491 uncertain significance not provided 2015-10-15 criteria provided, single submitter clinical testing This variant is denoted MLH1 c.2024G>A at the cDNA level and p.Ser675Asn (S675N) at the protein level, and results in the change of a Serine to an Asparagine (AGC>AAC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Serine and Asparagine share similar properties, this is considered a conservative amino acid substitution. MLH1 Ser675Asn occurs at a position that is conserved in mammals and is located in a region that is required for interaction with PMS2, MLH3 and PMS1 (Pang 1997, Raevaara 2005). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether MLH1 Ser675Asn is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000580085 SCV000684790 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-04 criteria provided, single submitter clinical testing

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