ClinVar Miner

Submissions for variant NM_015627.3(LDLRAP1):c.67G>C (p.Gly23Arg)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002369482 SCV002664077 uncertain significance Cardiovascular phenotype 2022-01-07 criteria provided, single submitter clinical testing The c.67G>C (p.G23R) alteration is located in exon 1 (coding exon 1) of the LDLRAP1 gene. This alteration results from a G to C substitution at nucleotide position 67, causing the glycine (G) at amino acid position 23 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003098385 SCV003460929 uncertain significance Hypercholesterolemia, familial, 4 2022-01-11 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 23 of the LDLRAP1 protein (p.Gly23Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LDLRAP1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003235715 SCV003933940 uncertain significance not specified 2023-05-23 criteria provided, single submitter clinical testing Variant summary: LDLRAP1 c.67G>C (p.Gly23Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 150532 control chromosomes (gnomAD, v3). 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.67G>C in individuals affected with Familial Hypercholesterolemia and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and both laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Genome-Nilou Lab RCV003098385 SCV004173345 uncertain significance Hypercholesterolemia, familial, 4 2023-04-11 criteria provided, single submitter clinical testing

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