Submissions for variant NM_025137.4(SPG11):c.304C>T (p.Pro102Ser)

gnomAD frequency: 0.00001  dbSNP: rs758322703

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000686707	SCV000814236	uncertain significance	Hereditary spastic paraplegia 11	2022-08-15	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 102 of the SPG11 protein (p.Pro102Ser). This variant is present in population databases (rs758322703, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SPG11-related conditions. ClinVar contains an entry for this variant (Variation ID: 566795). 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"). 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.
CeGaT Center for Human Genetics Tuebingen	RCV000761910	SCV000892130	uncertain significance	not provided	2018-06-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000686707	SCV001275708	uncertain significance	Hereditary spastic paraplegia 11	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Fondazione Stella Maris	RCV001644765	SCV001519262	uncertain significance	Spastic ataxia	2021-01-04	criteria provided, single submitter	research
Ambry Genetics	RCV002442422	SCV002754116	uncertain significance	Inborn genetic diseases	2020-01-08	criteria provided, single submitter	clinical testing	The p.P102S variant (also known as c.304C>T), located in coding exon 2 of the SPG11 gene, results from a C to T substitution at nucleotide position 304. The proline at codon 102 is replaced by serine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab	RCV002468001	SCV002762901	uncertain significance	Amyotrophic lateral sclerosis type 5		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002468002	SCV002762902	uncertain significance	Charcot-Marie-Tooth disease axonal type 2X		criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000686707	SCV002762903	uncertain significance	Hereditary spastic paraplegia 11		criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000761910	SCV005409933	uncertain significance	not provided	2023-12-20	criteria provided, single submitter	clinical testing	PM2_moderate