ClinVar Miner

Submissions for variant NM_032415.7(CARD11):c.583G>C (p.Val195Leu)

gnomAD frequency: 0.00004  dbSNP: rs747351557
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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 RCV001230826 SCV001403323 likely benign Severe combined immunodeficiency due to CARD11 deficiency; BENTA disease 2024-01-29 criteria provided, single submitter clinical testing
Baylor Genetics RCV001332678 SCV001525063 uncertain significance BENTA disease 2020-01-21 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genetic Services Laboratory, University of Chicago RCV001819930 SCV002067449 uncertain significance not specified 2020-07-20 criteria provided, single submitter clinical testing DNA sequence analysis of the CARD11 gene demonstrated a sequence change, c.583G>C, in exon 5 that results in an amino acid change, p.Val195Leu. This sequence change has been described in the gnomAD database with a frequency of 0.024% in the European sub-population (dbSNP rs747351557). The p.Val195Leu change has been reported in the heterozygous state in a patient with atopic dermatitis, asthma, diverticulitis, and Type 2 diabetes (PMID: 30170123). In vitro studies demonstrated reduced protein activation, suggesting a loss of function mechanism (PMID: 30170123). The p.Val195Leu change affects a moderately conserved amino acid residue located in a domain of the CARD11 protein that is not known to be functional. The p.Val195Leu substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences, the clinical significance of the p.Val195Leu change remains unknown at this time.

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