Submissions for variant NM_001352514.2(HLCS):c.2151C>G (p.Asn717Lys)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002469975	SCV002766027	uncertain significance	not specified	2022-11-16	criteria provided, single submitter	clinical testing	Variant summary: HLCS c.1710C>G (p.Asn570Lys) results in a non-conservative amino acid change located in the catalytic domain (IPR004143) 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 4e-06 in 251488 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1710C>G has been reported in the literature in the compound heterozygous state together with a pathogenic variant in an individual affected with Holocarboxylase Synthetase Deficiency (Donti_2016). These data do not allow any strong conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.