Submissions for variant NM_001379500.1(COL18A1):c.1507G>A (p.Gly503Ser)

gnomAD frequency: 0.00001  dbSNP: rs368194132

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000388348	SCV000436384	uncertain significance	Knobloch syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001865237	SCV002199809	uncertain significance	not provided	2022-10-25	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 503 of the COL18A1 protein (p.Gly503Ser). This variant is present in population databases (rs368194132, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with COL18A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 340223). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Ambry Genetics	RCV004021852	SCV004927457	uncertain significance	Inborn genetic diseases	2023-10-14	criteria provided, single submitter	clinical testing	The c.1507G>A (p.G503S) alteration is located in exon 13 (coding exon 13) of the COL18A1 gene. This alteration results from a G to A substitution at nucleotide position 1507, causing the glycine (G) at amino acid position 503 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.