Submissions for variant NM_000090.4(COL3A1):c.3937A>C (p.Lys1313Gln)

gnomAD frequency: 0.00006  dbSNP: rs886038983

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001188120	SCV000319481	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2015-03-12	criteria provided, single submitter	clinical testing	The p.K1313Q variant (also known as c.3937A>C), located in coding exon 49 of the COL3A1 gene, results from an A to C substitution at nucleotide position 3937. The lysine at codon 1313 is replaced by glutamine, an amino acid with some similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is completely conserved on sequence alignment. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV000765599	SCV000896916	uncertain significance	Ehlers-Danlos syndrome, type 4	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000765599	SCV000940294	uncertain significance	Ehlers-Danlos syndrome, type 4	2023-11-14	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1313 of the COL3A1 protein (p.Lys1313Gln). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 263935). 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 with a negative predictive value of 95%. 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.
Color Diagnostics, LLC DBA Color Health	RCV001188120	SCV001355093	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-04-20	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with glutamine at codon 1313 of the COL3A1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with COL3A1-related disorders in the literature. This variant has been identified in 3/282832 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV003456388	SCV004183848	uncertain significance	not provided	2023-11-01	criteria provided, single submitter	clinical testing	COL3A1: PM5, PM2:Supporting
All of Us Research Program, National Institutes of Health	RCV000765599	SCV004825531	uncertain significance	Ehlers-Danlos syndrome, type 4	2024-04-16	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with glutamine at codon 1313 of the COL3A1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 3/282832 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.