NM_004092.4(ECHS1):c.72G>A (p.Trp24Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 6, 2023
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:: RCV003770398.2

Allele description [Variation Report for NM_004092.4(ECHS1):c.72G>A (p.Trp24Ter)]

NM_004092.4(ECHS1):c.72G>A (p.Trp24Ter)

Genes:

LOC130005023:ATAC-STARR-seq lymphoblastoid silent region 2977 [Gene]
ECHS1:enoyl-CoA hydratase, short chain 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q26.3

Genomic location:

Preferred name:

NM_004092.4(ECHS1):c.72G>A (p.Trp24Ter)

HGVS:

NC_000010.11:g.133373262C>T
NG_042077.1:g.5143G>A
NM_004092.4:c.72G>AMANE SELECT
NP_004083.3:p.Trp24Ter
NC_000010.10:g.135186766C>T
NC_000010.10:g.135186766C>T

Protein change:

W24*

Links:

dbSNP: rs776926045

NCBI 1000 Genomes Browser:

rs776926045

Molecular consequence:

NM_004092.4:c.72G>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV004641024	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 6, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25393721, 26000322, 27090768, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004641024

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 6, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome.

Sakai C, Yamaguchi S, Sasaki M, Miyamoto Y, Matsushima Y, Goto Y.

Hum Mutat. 2015 Feb;36(2):232-9. doi: 10.1002/humu.22730.

PubMed [citation]

PMID:: 25393721

Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.

Haack TB, Jackson CB, Murayama K, Kremer LS, Schaller A, Kotzaeridou U, de Vries MC, Schottmann G, Santra S, Büchner B, Wieland T, Graf E, Freisinger P, Eggimann S, Ohtake A, Okazaki Y, Kohda M, Kishita Y, Tokuzawa Y, Sauer S, Memari Y, Kolb-Kokocinski A, et al.

Ann Clin Transl Neurol. 2015 May;2(5):492-509. doi: 10.1002/acn3.189. Epub 2015 Mar 13.

PubMed [citation]

PMID:: 26000322
PMCID:: PMC4435704

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004641024.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Trp24*) in the ECHS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ECHS1 are known to be pathogenic (PMID: 25393721, 26000322, 27090768). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with ECHS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 986371). For these reasons, this variant has been classified as Pathogenic.

#	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: Sep 29, 2024

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