Submissions for variant NM_003119.4(SPG7):c.270A>C (p.Arg90Ser)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002685660	SCV002984104	uncertain significance	Hereditary spastic paraplegia 7	2022-06-15	criteria provided, single submitter	clinical testing	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. 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 SPG7 protein function. This variant has not been reported in the literature in individuals affected with SPG7-related conditions. This variant is present in population databases (rs762017481, gnomAD 0.002%). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 90 of the SPG7 protein (p.Arg90Ser).
Ambry Genetics	RCV002685661	SCV003615147	uncertain significance	Inborn genetic diseases	2022-02-10	criteria provided, single submitter	clinical testing	The c.270A>C (p.R90S) alteration is located in exon 2 (coding exon 2) of the SPG7 gene. This alteration results from a A to C substitution at nucleotide position 270, causing the arginine (R) at amino acid position 90 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.