ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.-121T>C (rs777716188)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000211691 SCV000294394 likely pathogenic Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge RCV000211691 SCV000599303 likely pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter curation
Color Health, Inc RCV000775225 SCV000909470 uncertain significance Familial hypercholesterolemia 2020-12-22 criteria provided, single submitter clinical testing This LDLR variant (c.-121T>C) causes a single nucleotide change in the promoter region (between the TATA and SP1 binding motifs) of the LDLR gene. Experimental studies in vitro of LDLR gene expression have shown a moderate decrease in LDLR gene expression (PMID: 25248394). However, clinical relevance of this observation is not clear. This variant has been reported in at least two individuals suspected of having familial hypercholesterolemia (PMID: 20236128, 22883975, 23669246). The genome region of this variant is not well covered in population databases and thus the frequency of this variant in the general population is unknown. Available evidence is insufficient to determine the pathogenicity of this variant conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Illumina Clinical Services Laboratory,Illumina RCV000211691 SCV001288136 uncertain significance Familial hypercholesterolemia 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Brunham Lab, Centre for Heart and Lung Innovation,University of British Columbia RCV000211691 SCV001432551 likely pathogenic Familial hypercholesterolemia 1 2018-12-06 criteria provided, single submitter research
Invitae RCV000775225 SCV001503764 uncertain significance Familial hypercholesterolemia 2020-09-01 criteria provided, single submitter clinical testing This variant occurs in a non-coding region of the LDLR gene. It does not change the encoded amino acid sequence of the LDLR protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has been observed in individual(s) with clinical features of familial hypercholesterolemia (PMID: 20236128, 24075752). ClinVar contains an entry for this variant (Variation ID: 226302). Experimental studies have shown that this variant affects LDLR transcription (PMID: 25248394). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Cardiovascular Genetics Laboratory,PathWest Laboratory Medicine WA - Fiona Stanley Hospital RCV000211691 SCV000268532 uncertain significance Familial hypercholesterolemia 1 2011-06-10 no assertion criteria provided clinical testing

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