NM_203446.3(SYNJ1):c.3749A>T (p.Gln1250Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 17, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001302392.8

Allele description [Variation Report for NM_203446.3(SYNJ1):c.3749A>T (p.Gln1250Leu)]

NM_203446.3(SYNJ1):c.3749A>T (p.Gln1250Leu)

Gene:

SYNJ1:synaptojanin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

21q22.11

Genomic location:

Preferred name:

NM_203446.3(SYNJ1):c.3749A>T (p.Gln1250Leu)

HGVS:

NC_000021.9:g.32639074T>A
NG_030017.2:g.93966A>T
NM_001160302.2:c.3701A>T
NM_001160306.2:c.3608A>T
NM_003895.4:c.3866A>T
NM_203446.3:c.3749A>TMANE SELECT
NP_001153774.1:p.Gln1234Leu
NP_001153774.1:p.Gln1234Leu
NP_001153778.1:p.Gln1203Leu
NP_003886.3:p.Gln1289Leu
NP_003886.3:p.Gln1289Leu
NP_982271.3:p.Gln1250Leu
NC_000021.8:g.34011384T>A
NG_030017.1:g.93968A>T
NM_001160302.1:c.3701A>T
NM_003895.3:c.3866A>T

Protein change:

Q1203L

Links:

dbSNP: rs1433204750

NCBI 1000 Genomes Browser:

rs1433204750

Molecular consequence:

NM_001160302.2:c.3701A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001160306.2:c.3608A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003895.4:c.3866A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_203446.3:c.3749A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Early-onset Parkinson disease 20
Identifiers:: MONDO: MONDO:0014233; MedGen: C3809824; Orphanet: 391411; OMIM: 615530

Name:: Developmental and epileptic encephalopathy, 53
Synonyms:: Epileptic encephalopathy, early infantile, 53
Identifiers:: MONDO: MONDO:0033362; MedGen: C4479313; OMIM: 617389

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001491600	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 17, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001491600

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 17, 2024)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001491600.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces glutamine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 1289 of the SYNJ1 protein (p.Gln1289Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SYNJ1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1005510). 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 SYNJ1 protein function with a negative predictive value of 80%. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 11, 2025

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