Submissions for variant NM_001354604.2(MITF):c.1150G>A (p.Ala384Thr)

dbSNP: rs202020443

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000825187	SCV000966461	likely benign	not specified	2018-05-08	criteria provided, single submitter	clinical testing	The p.Ala379Thr variant in exon 9 of MITF is not expected to have clinical signi ficance because it has been identified in 0.04% (13/30746) and computational pre diction tools and conservation analyses suggest that this variant may not impact the protein. ACMG/AMP Criteria applied: BS1_Supporting, BP4.
GeneDx	RCV001580031	SCV001811065	uncertain significance	not provided	2024-02-12	criteria provided, single submitter	clinical testing	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	RCV002538209	SCV003265975	uncertain significance	Tietz syndrome; Waardenburg syndrome type 2A; Melanoma, cutaneous malignant, susceptibility to, 8	2024-01-30	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 277 of the MITF protein (p.Ala277Thr). This variant is present in population databases (rs202020443, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with MITF-related conditions. ClinVar contains an entry for this variant (Variation ID: 666714). 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 not expected to disrupt MITF protein function with a negative predictive value of 80%. 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.
Revvity Omics, Revvity	RCV001580031	SCV003808812	uncertain significance	not provided	2022-03-23	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001580031	SCV004150466	uncertain significance	not provided	2023-09-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001580031	SCV001809433	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001580031	SCV001973787	likely benign	not provided		no assertion criteria provided	clinical testing