ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1061-1G>C (rs879254774)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237908 SCV000295189 likely pathogenic Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000237908 SCV000599359 pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter curation
Invitae RCV000791381 SCV000826465 likely pathogenic Familial hypercholesterolemia 2018-12-19 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 7 of the LDLR gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported as homozygous in an individual with clinical features of homozygous familial hypercholesterolemia (HoFH) (PMID: 10487495). A different nucleotide change at the same position, c.1061-1G>A, has also been reported in individuals with familial hypercholesterolemia (PMID: 17539906). ClinVar contains an entry for this variant (Variation ID: 251637). Experimental studies have shown that this sequence change results in two alternate RNA splicing mechanisms that cause either skipping of exon 8, in which the integrity of the reading frame is preserved, or the creation of a premature translational stop signal in exon 8 (PMID: 10487495). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000786158 SCV000924841 likely pathogenic not provided 2018-01-29 no assertion criteria provided provider interpretation

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