Submissions for variant NM_004312.3(ARR3):c.1052C>T (p.Pro351Leu)

dbSNP: rs140505250

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Paul Sabatier University EA-4555, Paul Sabatier University	RCV000207379	SCV000259140	likely benign	Anophthalmia-microphthalmia syndrome	2013-01-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001573333	SCV002254853	uncertain significance	not provided	2021-09-02	criteria provided, single submitter	clinical testing	This sequence change replaces proline with leucine at codon 351 of the ARR3 protein (p.Pro351Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs140505250, ExAC 0.06%). This variant has not been reported in the literature in individuals affected with ARR3-related conditions. ClinVar contains an entry for this variant (Variation ID: 221943). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001573333	SCV001799042	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001573333	SCV001971517	uncertain significance	not provided		no assertion criteria provided	clinical testing