ClinVar Miner

Submissions for variant NM_001127713.1(ATL1):c.1243C>T (p.Arg415Trp) (rs119476050)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000190652 SCV000244092 likely pathogenic Inborn genetic diseases 2014-07-16 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected
Invitae RCV000004600 SCV000551414 pathogenic Hereditary spastic paraplegia 3A 2019-12-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 415 of the ATL1 protein (p.Arg415Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs119476050, ExAC 0.001%). This variant has been reported in several individuals affected with hereditary spastic paraplegia (PMID: 20932283, 24451228, 19459885, 16401858). This variant has also been reported to segregate with hereditary spastic paraplegia in several families; however, it has also been identified in unaffected family members due to adult onset and incomplete penetrance (PMID: 15184642, 24417445, 23483706, 26671083). ClinVar contains an entry for this variant (Variation ID: 4352). This missense change is located in a region of the ATL1 protein where a significant number of previously reported ATL1 missense mutations are found (PMID: 15596607, 20932283, 25454648, 23483706, 21336785, 19768483). These observations suggest that a previously unreported missense substitution within this region may affect protein function, but experiments have not been done to test this possibility. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001090532 SCV001246136 pathogenic not provided 2019-10-01 criteria provided, single submitter clinical testing
OMIM RCV000004600 SCV000024774 pathogenic Hereditary spastic paraplegia 3A 2013-06-01 no assertion criteria provided literature only
GeneReviews RCV000004600 SCV000041287 pathologic Hereditary spastic paraplegia 3A 2010-09-21 no assertion criteria provided curation Converted during submission to Pathogenic.

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