NM_000026.4(ADSL):c.340T>C (p.Tyr114His) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 24, 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:: RCV000186703.29

Allele description [Variation Report for NM_000026.4(ADSL):c.340T>C (p.Tyr114His)]

NM_000026.4(ADSL):c.340T>C (p.Tyr114His)

Gene:

ADSL:adenylosuccinate lyase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.1

Genomic location:

Preferred name:

NM_000026.4(ADSL):c.340T>C (p.Tyr114His)

Other names:

p.Y114H:TAT>CAT

HGVS:

NC_000022.11:g.40350018T>C
NG_007993.2:g.8519T>C
NM_000026.4:c.340T>CMANE SELECT
NM_001123378.3:c.340T>C
NM_001317923.2:c.148T>C
NM_001363840.3:c.340T>C
NP_000017.1:p.Tyr114His
NP_001116850.1:p.Tyr114His
NP_001304852.1:p.Tyr50His
NP_001350769.1:p.Tyr114His
NC_000022.10:g.40746022T>C
NM_000026.2:c.340T>C
NM_000026.3:c.340T>C
NR_134256.2:n.399T>C
P30566:p.Tyr114His

Protein change:

Y114H

Links:

UniProtKB: P30566#VAR_017080; dbSNP: rs374259530

NCBI 1000 Genomes Browser:

rs374259530

Molecular consequence:

NM_000026.4:c.340T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001123378.3:c.340T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001317923.2:c.148T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363840.3:c.340T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_134256.2:n.399T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000240269	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jan 24, 2022)	germline	clinical testing	Citation Link,
SCV001249556	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Feb 1, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000240269

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jan 24, 2022)

germline

clinical testing

Citation Link,

SCV001249556

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Feb 1, 2017)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000240269.16

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

Description

Published functional studies demonstrate pronounced protein instability and significantly reduced or absent enzyme activity (Kmoch et al., 2000; Zikanova et al., 2010); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 20127976, 22812634, 16839792, 10888601, 18524658, 29655203, 31467849, 31623504, 22180458, 31589614, 17188615, 33648541)

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

From CeGaT Center for Human Genetics Tuebingen, SCV001249556.26

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

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

Last Updated: Oct 20, 2024

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