Submissions for variant NM_006521.6(TFE3):c.350G>A (p.Arg117Gln)

dbSNP: rs2147777346

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes	RCV001374939	SCV001572227	pathogenic	Neurodevelopmental disorder	2020-03-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001568602	SCV001792506	pathogenic	not provided	2024-12-04	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31833172, 33504798, 32409512, 33057194, 35982159)
CeGaT Center for Human Genetics Tuebingen	RCV001568602	SCV005074892	pathogenic	not provided	2024-09-01	criteria provided, single submitter	clinical testing	TFE3: PS2:Very Strong, PM2, PS4:Moderate
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV001732146	SCV005398333	pathogenic	Intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies	2024-10-08	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established. Gain of function is the suggested mechanism of disease and is associated with intellectual developmental disorder, X-linked syndromic, with pigmentary mosaicism and coarse facies (MIM#301066; PMID: 30595499). 0110 - This gene is associated with X-linked dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to glutamine. (I) 0253 - This variant is hemizygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated MITF/TFEB/TFEC/TFE3 N-terminus domain (DECIPHER). (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been classified as pathogenic by multiple clinical laboratories in ClinVar. This variant has also been observed in heterozygous and hemizygous de novo individuals (one of which was mosaic) with TFE3-related symptoms (PMID: 31833172, 32409512). (SP) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001568602	SCV001807707	pathogenic	not provided		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001568602	SCV001963576	pathogenic	not provided		no assertion criteria provided	clinical testing
OMIM	RCV001732146	SCV001984765	pathogenic	Intellectual developmental disorder, X-linked, syndromic, with pigmentary mosaicism and coarse facies	2021-10-27	no assertion criteria provided	literature only