Submissions for variant NM_004208.4(AIFM1):c.1592A>T (p.Glu531Val)

dbSNP: rs1285480966

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001764888	SCV001989400	uncertain significance	not provided	2024-04-03	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV002539937	SCV002966715	uncertain significance	Charcot-Marie-Tooth Neuropathy X; Combined oxidative phosphorylation deficiency	2022-12-15	criteria provided, single submitter	clinical testing	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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AIFM1 protein function. ClinVar contains an entry for this variant (Variation ID: 1304652). This variant has not been reported in the literature in individuals affected with AIFM1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 531 of the AIFM1 protein (p.Glu531Val).
PreventionGenetics, part of Exact Sciences	RCV003401677	SCV004104412	uncertain significance	AIFM1-related disorder	2023-07-09	criteria provided, single submitter	clinical testing	The AIFM1 c.1592A>T variant is predicted to result in the amino acid substitution p.Glu531Val. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
CeGaT Center for Human Genetics Tuebingen	RCV001764888	SCV005075658	uncertain significance	not provided	2024-06-01	criteria provided, single submitter	clinical testing	AIFM1: PM2