ClinVar Miner

Submissions for variant NM_015627.3(LDLRAP1):c.406C>T (p.Gln136Ter)

gnomAD frequency: 0.00001  dbSNP: rs121908325
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000005041 SCV000938785 pathogenic Hypercholesterolemia, familial, 4 2024-10-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln136*) in the LDLRAP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LDLRAP1 are known to be pathogenic (PMID: 11326085, 12464675). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with familial hypercholesterolemia (PMID: 11326085, 27247956). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 4775). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV000005041 SCV002017139 pathogenic Hypercholesterolemia, familial, 4 2020-03-24 criteria provided, single submitter clinical testing
Ambry Genetics RCV002321472 SCV002631375 pathogenic Cardiovascular phenotype 2022-03-18 criteria provided, single submitter clinical testing The p.Q136* pathogenic mutation (also known as c.406C>T), located in coding exon 4 of the LDLRAP1 gene, results from a C to T substitution at nucleotide position 406. This changes the amino acid from a glutamine to a stop codon within coding exon 4. This alteration has been described in homozygous state in families with familial hypercholesterolemia (Garcia CK et al. Science, 2001 May;292:1394-8; Soufi M et al. Gene, 2013 May;521:200-3; Fahed AC et al. Mol Genet Genomic Med, 2016 May;4:283-91). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Genome-Nilou Lab RCV000005041 SCV004173951 pathogenic Hypercholesterolemia, familial, 4 2023-04-11 criteria provided, single submitter clinical testing
OMIM RCV000005041 SCV000025217 pathogenic Hypercholesterolemia, familial, 4 2001-05-18 no assertion criteria provided literature only
Natera, Inc. RCV001826419 SCV002085931 pathogenic Familial hypercholesterolemia 2020-08-11 no assertion criteria provided clinical testing

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