Submissions for variant NM_003060.4(SLC22A5):c.254_264dup (p.Ile89fs)

dbSNP: rs377767449

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000186155	SCV000239181	pathogenic	not provided	2023-12-27	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 16652335, 31980526, 11715001, 21922592, 23379544, 28841266, 15714519)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000022309	SCV000698147	pathogenic	Renal carnitine transport defect	2016-08-04	criteria provided, single submitter	clinical testing	Variant summary: The SLC22A5 c.254_264dup11 (p.Ile89Glyfs) variant results in a premature termination codon, predicted to cause a truncated or absent SLC22A5 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant is absent in 42704 control chromosomes. This variant has been reported in multiple PCD patients both homozygously and heterozygously. Functional study showed this variant caused decreased levels of mature mRNA. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000022309	SCV000960663	pathogenic	Renal carnitine transport defect	2024-10-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ile89Glyfs*45) in the SLC22A5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC22A5 are known to be pathogenic (PMID: 9916797). This variant is present in population databases (rs757431170, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with primary carnitine deficiency (PMID: 11715001, 28841266). ClinVar contains an entry for this variant (Variation ID: 38790). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000186155	SCV001247709	pathogenic	not provided	2020-01-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000022309	SCV002055797	pathogenic	Renal carnitine transport defect	2021-07-15	criteria provided, single submitter	clinical testing
Mendelics	RCV000022309	SCV002519751	pathogenic	Renal carnitine transport defect	2022-05-04	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000022309	SCV002785724	pathogenic	Renal carnitine transport defect	2024-05-04	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000022309	SCV004201245	pathogenic	Renal carnitine transport defect	2024-03-16	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV002226450	SCV002078287	pathogenic	Decreased circulating carnitine concentration	2020-08-26	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000022309	SCV002107410	pathogenic	Renal carnitine transport defect	2020-08-26	no assertion criteria provided	clinical testing
Ricardo Maselli Laboratory, University of California Davis	RCV003483445	SCV004231839	pathogenic	Congenital myasthenic syndrome 20	2024-01-16	no assertion criteria provided	clinical testing	Congenital Myasthenic Syndrome with episodic apneas.