U.S. flag

An official website of the United States government

NM_015378.4(VPS13D):c.3569G>A (p.Gly1190Asp) AND not provided

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Nov 21, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001816689.6

Allele description [Variation Report for NM_015378.4(VPS13D):c.3569G>A (p.Gly1190Asp)]

NM_015378.4(VPS13D):c.3569G>A (p.Gly1190Asp)

Gene:
VPS13D:vacuolar protein sorting 13 homolog D [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p36.22
Genomic location:
Preferred name:
NM_015378.4(VPS13D):c.3569G>A (p.Gly1190Asp)
HGVS:
  • NC_000001.11:g.12277157G>A
  • NG_056877.1:g.52119G>A
  • NM_015378.4:c.3569G>AMANE SELECT
  • NM_018156.4:c.3569G>A
  • NP_056193.2:p.Gly1190Asp
  • NP_060626.2:p.Gly1190Asp
  • LRG_1213t1:c.3569G>A
  • LRG_1213:g.52119G>A
  • LRG_1213p1:p.Gly1190Asp
  • NC_000001.10:g.12337214G>A
  • NM_015378.2:c.3569G>A
Protein change:
G1190D; GLY1190ASP
Links:
OMIM: 608877.0001; dbSNP: rs1557680919
NCBI 1000 Genomes Browser:
rs1557680919
Molecular consequence:
  • NM_015378.4:c.3569G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_018156.4:c.3569G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002067483Genetic Services Laboratory, University of Chicago
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Apr 13, 2020)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002978509Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Nov 21, 2022)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Mutations in VPS13D lead to a new recessive ataxia with spasticity and mitochondrial defects.

Seong E, Insolera R, Dulovic M, Kamsteeg EJ, Trinh J, Brüggemann N, Sandford E, Li S, Ozel AB, Li JZ, Jewett T, Kievit AJA, Münchau A, Shakkottai V, Klein C, Collins CA, Lohmann K, van de Warrenburg BP, Burmeister M.

Ann Neurol. 2018 Jun;83(6):1075-1088. doi: 10.1002/ana.25220. Epub 2018 Jun 30.

PubMed [citation]
PMID:
29604224
PMCID:
PMC6105379
See all PubMed Citations (3)

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV002067483.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV002978509.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. 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 VPS13D protein function. ClinVar contains an entry for this variant (Variation ID: 561198). This missense change has been observed in individual(s) with VPS13D-related conditions (PMID: 29604224). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1190 of the VPS13D protein (p.Gly1190Asp).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 5, 2024