ClinVar Miner

Submissions for variant NM_001734.5(C1S):c.1139C>T (p.Ser380Phe)

gnomAD frequency: 0.00001  dbSNP: rs782329906
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Leipzig Medical Center RCV001253335 SCV001428995 uncertain significance Ehlers-Danlos syndrome, periodontal type 2 2018-08-29 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001281033 SCV001468449 uncertain significance Complement component C1s deficiency; Ehlers-Danlos syndrome, periodontal type 2 2021-03-30 criteria provided, single submitter clinical testing C1S NM_201442.3 exon 10 p.Ser380Phe (c.1139C>T):This variant has not been reported in the literature but is present in 0.002% (3/113702) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/12-7175019-C-T?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:976135). Evolutionary conservation suggests that this variant may not impact the protein; computational predictive tools for this variant are unclear. 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 RCV002568731 SCV003266714 uncertain significance not provided 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 380 of the C1S protein (p.Ser380Phe). This variant is present in population databases (rs782329906, gnomAD 0.003%). 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: 976135). 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 expected to disrupt C1S protein function with a positive 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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