ClinVar Miner

Submissions for variant NM_002528.7(NTHL1):c.685+1G>A (rs372946560)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000807122 SCV000947161 pathogenic not provided 2018-10-09 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the NTHL1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs372946560, ExAC 0.002%). This variant has been observed on the opposite chromosome (in trans) from another pathogenic variant in an individual affected with multiple primary tumors including multiple colorectal adenomas (PMID: 26559593). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 218092). Experimental studies have shown that this sequence change disrupts normal mRNA splicing (PMID: 26559593). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in NTHL1 are known to be pathogenic (PMID: 25938944, 26559593). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000202319 SCV000257324 pathogenic Familial adenomatous polyposis 3 2015-11-12 no assertion criteria provided literature only

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