ClinVar Miner

Submissions for variant NM_001849.3(COL6A2):c.1336G>A (p.Asp446Asn) (rs535007570)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000232259 SCV000226456 likely benign not specified 2016-12-25 criteria provided, single submitter clinical testing
Center for Genetic Medicine Research,Children's National Medical Center RCV000232259 SCV000265832 uncertain significance not specified 2015-12-01 criteria provided, single submitter research
Illumina Clinical Services Laboratory,Illumina RCV000391113 SCV000436685 benign Collagen VI-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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000300525 SCV000436686 likely benign Myosclerosis, autosomal recessive 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000766827 SCV000618570 uncertain significance not provided 2021-03-30 criteria provided, single submitter clinical testing Reported as a variant of uncertain clinical significance in an individual with limb-girdle muscular dystrophy in published literature (Punetha et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27854218, 23040494, 30564623)
Invitae RCV000544905 SCV000657101 uncertain significance Bethlem myopathy 1 2020-06-13 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 446 of the COL6A2 protein (p.Asp446Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs535007570, ExAC 0.1%). This variant has been reported in the heterozygous state in individuals with clinical suspicion of limb-girdle muscular dystrophy (LGMD) (PMID: 27854218, 30564623) and in an unaffected control individual (PMID: 23040494). ClinVar contains an entry for this variant (Variation ID: 194621). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). 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 RCV001267221 SCV001445402 uncertain significance Inborn genetic diseases 2015-03-06 criteria provided, single submitter clinical testing
Clinical Genetics,Academic Medical Center RCV000766827 SCV001921808 uncertain significance not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000766827 SCV001951186 uncertain significance not provided no assertion criteria provided clinical testing

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