ClinVar Miner

Submissions for variant NM_001379610.1(SPINK1):c.208T>A (p.Ser70Thr)

gnomAD frequency: 0.00006  dbSNP: rs373011963
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000691476 SCV000819256 uncertain significance Hereditary pancreatitis 2022-06-30 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 570585). This variant has not been reported in the literature in individuals affected with SPINK1-related conditions. This variant is present in population databases (rs373011963, gnomAD 0.03%). This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 70 of the SPINK1 protein (p.Ser70Thr). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV000691476 SCV001175097 likely benign Hereditary pancreatitis 2024-03-21 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526013 SCV005039556 uncertain significance not specified 2024-03-11 criteria provided, single submitter clinical testing Variant summary: SPINK1 c.208T>A (p.Ser70Thr) results in a conservative amino acid change located in the Kazal domain (IPR002350) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 250554 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.208T>A in individuals affected with Chronic Pancreatitis Risk and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 570585). Based on the evidence outlined above, the variant was classified as uncertain significance.

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