Submissions for variant NM_005055.5(RAPSN):c.902C>T (p.Ala301Val)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002917407	SCV003247396	uncertain significance	Fetal akinesia deformation sequence 1; Congenital myasthenic syndrome 11	2021-08-31	criteria provided, single submitter	clinical testing	This sequence change replaces alanine with valine at codon 301 of the RAPSN protein (p.Ala301Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs778113748, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with RAPSN-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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	RCV003134527	SCV003813716	uncertain significance	not provided	2019-05-14	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004066072	SCV004936877	uncertain significance	Inborn genetic diseases	2024-02-28	criteria provided, single submitter	clinical testing	The c.902C>T (p.A301V) alteration is located in exon 5 (coding exon 5) of the RAPSN gene. This alteration results from a C to T substitution at nucleotide position 902, causing the alanine (A) at amino acid position 301 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV004733538	SCV005363398	uncertain significance	RAPSN-related disorder	2024-03-09	no assertion criteria provided	clinical testing	The RAPSN c.902C>T variant is predicted to result in the amino acid substitution p.Ala301Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.015% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.