Submissions for variant NM_032242.4(PLXNA1):c.3316G>A (p.Ala1106Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002952936	SCV003272355	uncertain significance	not provided	2022-05-18	criteria provided, single submitter	clinical testing	This variant is present in population databases (rs369260755, gnomAD 0.01%). 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. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with PLXNA1-related conditions. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1106 of the PLXNA1 protein (p.Ala1106Thr).
PreventionGenetics, part of Exact Sciences	RCV003409976	SCV004113225	uncertain significance	PLXNA1-related disorder	2024-07-30	no assertion criteria provided	clinical testing	The PLXNA1 c.3316G>A variant is predicted to result in the amino acid substitution p.Ala1106Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.012% of alleles in individuals of European (Non-Finnish) descent in gnomAD. A different variant affecting the same amino acid (p.Ala1106Val) was reported as uncertain in one individual with hypogonadotropic hypogonadism, who also carried a variant in the NR0B1 gene (Tables 1 & 2, Men et al. 2021. PubMed ID: 34636164 ). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.