ClinVar Miner

Submissions for variant NM_000094.3(COL7A1):c.4559C>T (p.Pro1520Leu) (rs140114392)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000922787 SCV001068230 likely benign not provided 2020-12-04 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001150557 SCV001311635 likely benign Dystrophic epidermolysis bullosa 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000922787 SCV001551847 uncertain significance not provided no assertion criteria provided clinical testing The COL7A1 p.Pro1520Leu variant was not identified in the literature nor was it identified in ClinVar or LOVD 3.0. The variant was identified in dbSNP (ID: rs140114392) and in control databases in 130 of 282088 chromosomes (1 homozygous) at a frequency of 0.0004608 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 106 of 24878 chromosomes (freq: 0.004261), Other in 5 of 7204 chromosomes (freq: 0.000694), Latino in 7 of 35420 chromosomes (freq: 0.000198), European (non-Finnish) in 10 of 128598 chromosomes (freq: 0.000078) and South Asian in 2 of 30588 chromosomes (freq: 0.000065), but was not observed in the Ashkenazi Jewish, East Asian, and European (Finnish) populations. The p.Pro1520 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) 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 (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) 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 although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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