Submissions for variant NM_177550.5(SLC13A5):c.441G>A (p.Met147Ile)

gnomAD frequency: 0.00004  dbSNP: rs764711084

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000556517	SCV000655333	uncertain significance	Developmental and epileptic encephalopathy, 25	2022-08-15	criteria provided, single submitter	clinical testing	This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 147 of the SLC13A5 protein (p.Met147Ile). This variant is present in population databases (rs764711084, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with SLC13A5-related conditions. ClinVar contains an entry for this variant (Variation ID: 475197). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV001764623	SCV001990527	uncertain significance	not provided	2019-07-29	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Genome-Nilou Lab	RCV000556517	SCV002055675	uncertain significance	Developmental and epileptic encephalopathy, 25	2021-07-15	criteria provided, single submitter	clinical testing
Department of Pediatrics, Samsung Medical Center, Samsung Medical Center	RCV001252851	SCV001163994	uncertain significance	Microcephaly		no assertion criteria provided	research