ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.2388C>T (p.Ile796=) (rs543852919)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000462919 SCV000544647 uncertain significance Familial hypercholesterolemia 1 2016-08-16 criteria provided, single submitter clinical testing
Robarts Research Institute,Western University RCV000462919 SCV000782938 likely benign Familial hypercholesterolemia 1 2018-01-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780381 SCV000917584 likely benign not specified 2018-08-20 criteria provided, single submitter clinical testing Variant summary: LDLR c.2388C>T (p.Ile796Ile) alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-05 in 277170 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2388C>T in individuals affected with Familial Hypercholesterolemia and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrences with other pathogenic variant(s) have been reported in our internal database (LDLR c.1118_1121dupGTGG, p.Tyr375fsX7), providing supporting evidence for a benign role. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely benign" and "uncertain significance." Based on the evidence outlined above, the variant was classified as likely benign.
Color RCV001182970 SCV001348607 likely benign Familial hypercholesterolemia 2018-12-05 criteria provided, single submitter clinical testing

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