ClinVar Miner

Submissions for variant NM_000251.2(MSH2):c.2730del (p.Gln910fs) (rs1553370880)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519753 SCV000618406 uncertain significance not provided 2017-04-11 criteria provided, single submitter clinical testing This deletion of one nucleotide in MSH2 is denoted c.2730delG at the cDNA level and p.Gln910HisfsX2 (Q910HfsX2) at the protein level. The normal sequence, with the base that is deleted in brackets, is AACA[delG]CTAA. The deletion causes a frameshift which changes a Glutamine to a Histidine at codon 910, and creates a premature stop codon at position 2 of the new reading frame. Due to the position of the variant, nonsense mediated decay is not expected to occur, but it might cause loss of normal protein function through protein truncation. The disrupted region at the end of the gene is located within the region of interaction with MSH6 and MSH3, the helix-turn-helix domain, and results in the loss of a residue involved in phosphoserine modification (Guerrette 1998, Lutzen 2008, Zhou 2013). MSH2 Gln910HisfsX2 was observed in at least one Ashkenazi Jewish individual undergoing whole genome sequencing as a control subject; no information was provided regarding their personal or family history of cancer (Carmi 2014). Based on currently available information, it is unclear whether this is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.

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