Submissions for variant NM_001352514.2(HLCS):c.664_667del (p.Gln222fs)

dbSNP: rs776431253

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001878143	SCV002167448	pathogenic	Holocarboxylase synthetase deficiency	2023-05-30	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with HLCS-related conditions. This variant is present in population databases (rs776431253, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Gln75Glyfs*182) in the HLCS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in HLCS are known to be pathogenic (PMID: 16134170).
Myriad Genetics, Inc.	RCV001878143	SCV002601790	likely pathogenic	Holocarboxylase synthetase deficiency	2021-11-29	criteria provided, single submitter	clinical testing	NM_000411.6(HLCS):c.223_226delCAAA(Q75Gfs*182) is expected to be pathogenic in the context of holocarboxylase synthetase deficiency. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in HLCS, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening.
Baylor Genetics	RCV001878143	SCV005059690	likely pathogenic	Holocarboxylase synthetase deficiency	2024-02-04	criteria provided, single submitter	clinical testing