Submissions for variant NM_001352514.2(HLCS):c.2113G>A (p.Glu705Lys)

gnomAD frequency: 0.00315  dbSNP: rs149736764

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000185945	SCV000238902	benign	not specified	2018-03-05	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000185945	SCV000539302	likely benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Gene assocaited with multiple carboxylase deficiency/ holocarboxylase synthetase deficiency - Affected infants often have difficulty feeding, breathing problems, a skin rash, hair loss (alopecia), and a lack of energy (lethargy).2 homo Europeans. Frequency of this variant is too high for the disorder ( estimated to affect 1 in 87,000 people)
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000625204	SCV000744130	likely benign	Holocarboxylase synthetase deficiency	2016-05-02	criteria provided, single submitter	clinical testing
Invitae	RCV000625204	SCV000756242	benign	Holocarboxylase synthetase deficiency	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000625204	SCV001296828	likely benign	Holocarboxylase synthetase deficiency	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Ambry Genetics	RCV004020252	SCV004882381	likely benign	Inborn genetic diseases	2021-04-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573888	SCV001800397	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001573888	SCV001925555	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000625204	SCV002083727	benign	Holocarboxylase synthetase deficiency	2019-12-04	no assertion criteria provided	clinical testing