ClinVar Miner

Submissions for variant NM_004958.4(MTOR):c.5663T>G (p.Phe1888Cys)

dbSNP: rs869312666
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000209915 SCV000265516 pathogenic Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome 2014-07-10 criteria provided, single submitter research
GeneDx RCV000523811 SCV000619645 pathogenic not provided 2023-08-21 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: 27830187, 32494756, 28554332, 35982159, 37035737)
CeGaT Center for Human Genetics Tuebingen RCV000523811 SCV001334591 likely pathogenic not provided 2020-05-01 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV000209915 SCV001429272 pathogenic Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome 2019-08-22 criteria provided, single submitter clinical testing
Invitae RCV000523811 SCV002142302 pathogenic not provided 2021-05-14 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MTOR protein function. This variant has been observed in individual(s) with clinical features of Smith-Kingsmore syndrome (PMID: 27830187). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 224083). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with cysteine at codon 1888 of the MTOR protein (p.Phe1888Cys). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and cysteine.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000209915 SCV003843223 pathogenic Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome 2021-05-25 criteria provided, single submitter clinical testing
OMIM RCV000209915 SCV000564177 pathogenic Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome 2020-09-16 no assertion criteria provided literature only

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