ClinVar Miner

Submissions for variant NM_006785.4(MALT1):c.1868C>T (p.Pro623Leu)

gnomAD frequency: 0.00001  dbSNP: rs1004957123
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002271939 SCV002556248 uncertain significance not specified 2022-06-29 criteria provided, single submitter clinical testing Variant summary: MALT1 c.1868C>T (p.Pro623Leu) results in a non-conservative amino acid change located in the MALT1 immunoglobulin-like domain (IPR041077) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 247778 control chromosomes (gnomAD). 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.1868C>T in individuals affected with Severe Combined Immunodeficiency and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV003096126 SCV002937355 uncertain significance Combined immunodeficiency due to MALT1 deficiency 2022-06-08 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 623 of the MALT1 protein (p.Pro623Leu). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with MALT1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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.

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