Submissions for variant NM_015915.5(ATL1):c.757G>A (p.Val253Ile)

dbSNP: rs864622520

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000206078	SCV000260948	pathogenic	Hereditary spastic paraplegia 3A	2023-09-26	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 253 of the ATL1 protein (p.Val253Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant hereditary spastic paraplegia (PMID: 15596607, 16401858, 17285536, 20932283, 24604904, 26208798). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 220424). 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 ATL1 protein function. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000235294	SCV000293530	likely pathogenic	not provided	2024-01-29	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 20932283, 26208798, 15596607, 34782662, 17285536, 34015694, 20718791, 16401858, 31236401, 23334294, 21194679, 36359747, 35578252, 24604904, 31594988)
CeGaT Center for Human Genetics Tuebingen	RCV000235294	SCV001149211	likely pathogenic	not provided	2022-12-01	criteria provided, single submitter	clinical testing	ATL1: PM1, PM2, PS4:Moderate
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000235294	SCV001447890	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Paris Brain Institute, Inserm - ICM	RCV000206078	SCV001451211	pathogenic	Hereditary spastic paraplegia 3A		criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000235294	SCV001716181	likely pathogenic	not provided	2019-08-05	criteria provided, single submitter	clinical testing	PS4_moderate, PM1, PM2
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847933	SCV002106242	pathogenic	Hereditary spastic paraplegia	2022-01-14	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000235294	SCV003813062	likely pathogenic	not provided	2021-11-18	criteria provided, single submitter	clinical testing
Inherited Neuropathy Consortium Ii, University Of Miami	RCV000206078	SCV004011957	uncertain significance	Hereditary spastic paraplegia 3A	2016-01-06	no assertion criteria provided	literature only