ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1323C>T (p.Ile441=) (rs5933)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000771544 SCV000627018 benign Familial hypercholesterolemia 2019-12-31 criteria provided, single submitter clinical testing
Robarts Research Institute,Western University RCV000548668 SCV000782912 benign Familial hypercholesterolemia 1 2018-01-02 criteria provided, single submitter clinical testing
Color RCV000771544 SCV000904105 likely benign Familial hypercholesterolemia 2017-07-17 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000781494 SCV000919572 benign not specified 2017-10-12 criteria provided, single submitter clinical testing Variant summary: The LDLR c.1323C>T (p.Ile441Ile) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 121/277028 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.004829 (116/24020). This frequency is about 4 times the estimated maximal expected allele frequency of a pathogenic LDLR variant (0.0012508), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. An internal LCA sample also carried a pathogenic variant LDLR c.590G>A/ p.Cys197Tyr, further supporting the benign nature of this variant. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Taken together, this variant is classified as benign.

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