ClinVar Miner

Submissions for variant NM_000246.4(CIITA):c.965C>T (p.Pro322Leu)

dbSNP: rs74806537
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001280287 SCV002254503 uncertain significance MHC class II deficiency 2022-03-14 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 322 of the CIITA protein (p.Pro322Leu). This variant is present in population databases (rs74806537, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CIITA-related conditions. ClinVar contains an entry for this variant (Variation ID: 991982). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV005408796 SCV002496052 uncertain significance Rheumatoid arthritis; MHC class II deficiency 1 criteria provided, single submitter clinical testing CIITA NM_000246.3 exon 10 p.Pro322Leu (c.965C>T):This variant has not been reported in the literature but is present in 0.03% (5/15276) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/16-10904771-C-T?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:991982). This variant amino acid Leucine (Leu) is present in 4 species (Ferret, Panda, Flying Fox, Megabat) and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain
Fulgent Genetics, Fulgent Genetics RCV002069483 SCV002776238 uncertain significance MHC class II deficiency; Rheumatoid arthritis 2022-01-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV003365299 SCV004064509 uncertain significance Inborn genetic diseases 2023-06-16 criteria provided, single submitter clinical testing The c.965C>T (p.P322L) alteration is located in exon 10 (coding exon 10) of the CIITA gene. This alteration results from a C to T substitution at nucleotide position 965, causing the proline (P) at amino acid position 322 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001280287 SCV001467453 likely benign MHC class II deficiency 2020-04-24 no assertion criteria provided clinical testing

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