Submissions for variant NM_003119.4(SPG7):c.1807G>A (p.Ala603Thr)

gnomAD frequency: 0.00004  dbSNP: rs370852816

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000516941	SCV000615434	uncertain significance	not specified	2017-02-13	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001121650	SCV001280290	uncertain significance	Hereditary spastic paraplegia 7	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001121650	SCV001541559	uncertain significance	Hereditary spastic paraplegia 7	2021-08-26	criteria provided, single submitter	clinical testing	This sequence change replaces alanine with threonine at codon 603 of the SPG7 protein (p.Ala603Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs370852816, ExAC 0.006%). This missense change has been observed in individual(s) with hereditary spastic paraplegia (PMID: 16534102). ClinVar contains an entry for this variant (Variation ID: 448472). 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: "Benign"; Align-GVGD: "Class C55"). 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.
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research	RCV001121650	SCV005044639	uncertain significance	Hereditary spastic paraplegia 7	2022-01-01	criteria provided, single submitter	research
Breakthrough Genomics, Breakthrough Genomics	RCV004691828	SCV005192934	uncertain significance	not provided		criteria provided, single submitter	not provided