ClinVar Miner

Submissions for variant NM_001352514.2(HLCS):c.2519G>C (p.Gly840Ala)

gnomAD frequency: 0.00001  dbSNP: rs764148793
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668654 SCV000793288 uncertain significance Holocarboxylase synthetase deficiency 2017-08-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001731866 SCV001983466 uncertain significance not specified 2021-09-17 criteria provided, single submitter clinical testing Variant summary: HLCS c.2078G>C (p.Gly693Ala) results in a non-conservative amino acid change located in the Biotin protein ligase, C-terminal (IPR003142) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250760 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2078G>C has been reported in the literature as a compound heterozygous genotype in at-least one individual affected with Holocarboxylase Synthetase Deficiency (example, Donti_2016) and has been subsequently cited by others (example, Watabe_2018, Zheng_2020). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance citing an overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV000668654 SCV005664085 likely pathogenic Holocarboxylase synthetase deficiency 2024-05-16 criteria provided, single submitter clinical testing

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