Submissions for variant NM_001244008.2(KIF1A):c.2979C>T (p.Ala993=)

gnomAD frequency: 0.01425  dbSNP: rs116297894

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000760168	SCV000429260	benign	Hereditary spastic paraplegia 30	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000117395	SCV000513402	benign	not specified	2015-04-24	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083185	SCV000638560	benign	Hereditary spastic paraplegia 30; Neuropathy, hereditary sensory, type 2C; Intellectual disability, autosomal dominant 9	2024-02-01	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000712145	SCV000842569	benign	not provided	2017-12-28	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002312170	SCV000846617	benign	Inborn genetic diseases	2016-05-11	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Center for Precision Medicine, Vanderbilt University Medical Center	RCV000760168	SCV000889986	uncertain significance	Hereditary spastic paraplegia 30	2018-03-16	criteria provided, single submitter	research
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000712145	SCV001474350	benign	not provided	2021-03-04	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847697	SCV002104846	likely benign	Hereditary spastic paraplegia	2021-06-13	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000712145	SCV004149668	benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	KIF1A: BP4, BP7, BS1, BS2
Genetic Services Laboratory, University of Chicago	RCV000117395	SCV000151592	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.