Submissions for variant NM_144599.5(NIPA1):c.681C>T (p.Leu227=)

gnomAD frequency: 0.00015  dbSNP: rs200282898

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001117930	SCV001276174	likely benign	Hereditary spastic paraplegia 6	2018-01-13	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001117930	SCV001666897	likely benign	Hereditary spastic paraplegia 6	2023-08-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847070	SCV002105430	uncertain significance	Hereditary spastic paraplegia	2020-01-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003456443	SCV004184440	likely benign	not provided	2025-01-01	criteria provided, single submitter	clinical testing	NIPA1: BP4, BP7