Submissions for variant NM_001849.4(COL6A2):c.1750C>T (p.Pro584Ser)

dbSNP: rs779979272

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000343903	SCV000334166	uncertain significance	not provided	2015-08-11	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000274714	SCV000436711	uncertain significance	Collagen 6-related myopathy	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.
Illumina Laboratory Services, Illumina	RCV000329938	SCV000436712	uncertain significance	Myosclerosis	2016-06-14	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000343903	SCV003832539	uncertain significance	not provided	2019-09-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004021112	SCV004929507	uncertain significance	Inborn genetic diseases	2021-10-27	criteria provided, single submitter	clinical testing	The c.1750C>T (p.P584S) alteration is located in exon 23 (coding exon 22) of the COL6A2 gene. This alteration results from a C to T substitution at nucleotide position 1750, causing the proline (P) at amino acid position 584 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV005090341	SCV005798145	uncertain significance	Bethlem myopathy 1A	2024-11-23	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 584 of the COL6A2 protein (p.Pro584Ser). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with COL6A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 282615). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt COL6A2 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.