Submissions for variant NM_000090.4(COL3A1):c.803T>C (p.Phe268Ser)

gnomAD frequency: 0.00001  dbSNP: rs1318892403

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589600	SCV000695379	uncertain significance	not provided	2016-01-04	criteria provided, single submitter	clinical testing	Variant summary: c.803T>C affects a conserved nucleotide, resulting in amino acid change from Phe to Ser. 4/5 in-silico tools predict this variant to be damaging. 5/5 programs in Alamut predict that this variant does not affect normal splicing. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions are not confirmed by experimental studies. This variant is not found in 121150 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Color Diagnostics, LLC DBA Color Health	RCV001178831	SCV001343375	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-12-05	criteria provided, single submitter	clinical testing	Variant of Uncertain Significance due to insufficient evidence: This missense variant is located in the triple-helical region of the COL3A1 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/245942 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the pathogenicity of this variant conclusively.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003522987	SCV004301186	uncertain significance	Ehlers-Danlos syndrome, type 4	2023-09-03	criteria provided, single submitter	clinical testing	This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 495547). 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 COL3A1 protein function. This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 268 of the COL3A1 protein (p.Phe268Ser). 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.