ClinVar Miner

Submissions for variant NM_000094.3(COL7A1):c.724G>A (p.Glu242Lys) (rs549872555)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000392510 SCV000445152 uncertain significance Dystrophic epidermolysis bullosa 2018-01-12 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.
Invitae RCV001355397 SCV001631433 likely benign not provided 2020-11-14 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001355397 SCV001550272 uncertain significance not provided no assertion criteria provided clinical testing The COL7A1 p.E242K variant was not identified in the literature but was identified in dbSNP (ID: rs549872555) and ClinVar (classified as uncertain significance by Illumina). The variant was identified in control databases in 48 of 249272 chromosomes at a frequency of 0.0001926, and was observed only in the South Asian population in 48 of 30572 chromosomes (freq: 0.001570) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.E242 residue is conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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