Submissions for variant NM_006343.3(MERTK):c.2435A>C (p.Tyr812Ser)

dbSNP: rs141361084

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000454548	SCV000539621	uncertain significance	not specified	2016-03-29	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Gene associated with RP - not related to our patient's phenotype. This variant is reported in one individual with Leber congenital amaurosis who carreid a homozygous frameshift variant in another RP gen- RPGRIP1 (Eisenberger_2013_24265693).
Eurofins Ntd Llc (ga)	RCV000727047	SCV000705158	uncertain significance	not provided	2017-01-12	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001331567	SCV001523630	uncertain significance	Retinitis pigmentosa 38	2020-06-03	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp	RCV000727047	SCV001541582	uncertain significance	not provided	2022-10-03	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 812 of the MERTK protein (p.Tyr812Ser). This variant is present in population databases (rs141361084, gnomAD 0.02%). This missense change has been observed in individual(s) with Leber congenital amaurosis (PMID: 24265693). ClinVar contains an entry for this variant (Variation ID: 403082). 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 MERTK protein function. 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	RCV000727047	SCV002759018	likely benign	not provided	2022-12-02	criteria provided, single submitter	clinical testing	Reported in an individual with Leber congenital amaurosis who also harbored a homozygous pathogenic variant in another gene responsible for this phenotype (Eisenberger et al., 2013); 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: 24265693)
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV001331567	SCV004806292	uncertain significance	Retinitis pigmentosa 38	2024-03-25	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004816671	SCV005072590	uncertain significance	Retinal dystrophy	2020-01-01	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000727047	SCV005187859	uncertain significance	not provided		criteria provided, single submitter	not provided