ClinVar Miner

Submissions for variant NM_001734.5(C1S):c.514G>A (p.Gly172Arg)

gnomAD frequency: 0.00001  dbSNP: rs375308014
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000767908 SCV000898555 uncertain significance Complement component C1s deficiency; Ehlers-Danlos syndrome, periodontal type 2 2021-03-30 criteria provided, single submitter clinical testing C1S NM_001734.4 exon 5 p.Gly172Arg (c.514G>A): This variant has not been reported in the literature but is present in 5/33576 Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs375308014). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV002533925 SCV002965661 uncertain significance not provided 2023-11-29 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 172 of the C1S protein (p.Gly172Arg). This variant is present in population databases (rs375308014, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with C1S-related conditions. ClinVar contains an entry for this variant (Variation ID: 625898). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt C1S protein function with a negative predictive value of 80%. 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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