NM_001349206.2(LPIN1):c.1807-2A>G AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Dec 26, 2023
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:: RCV001990266.5

Allele description [Variation Report for NM_001349206.2(LPIN1):c.1807-2A>G]

NM_001349206.2(LPIN1):c.1807-2A>G

Gene:

LPIN1:lipin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p25.1

Genomic location:

Preferred name:

NM_001349206.2(LPIN1):c.1807-2A>G

HGVS:

NC_000002.12:g.11795406A>G
NG_012843.2:g.122828A>G
NM_001261427.3:c.1717-2A>G
NM_001261428.3:c.1954-2A>G
NM_001349199.2:c.1699-2A>G
NM_001349200.2:c.1777-2A>G
NM_001349201.2:c.1777-2A>G
NM_001349202.2:c.1804-2A>G
NM_001349203.2:c.1804-2A>G
NM_001349204.2:c.1807-2A>G
NM_001349205.2:c.1807-2A>G
NM_001349206.2:c.1807-2A>GMANE SELECT
NM_001349207.2:c.1897-2A>G
NM_001349208.2:c.1846-2A>G
NM_145693.4:c.1699-2A>G
NC_000002.11:g.11935532A>G

Links:

dbSNP: rs533651991

NCBI 1000 Genomes Browser:

rs533651991

Molecular consequence:

NM_001261427.3:c.1717-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001261428.3:c.1954-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001349199.2:c.1699-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001349200.2:c.1777-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001349201.2:c.1777-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001349202.2:c.1804-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001349203.2:c.1804-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001349204.2:c.1807-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001349205.2:c.1807-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001349206.2:c.1807-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001349207.2:c.1897-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001349208.2:c.1846-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_145693.4:c.1699-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

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
SCV002249553	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 26, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 16199547, 18817903, 20583302, 22481384, 26111941, 35242575, 28492532
SCV004226539	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 10, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 35242575, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002249553

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 26, 2023)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV004226539

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 10, 2022)

germline

clinical testing

PubMed (2)
[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	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood.

Zeharia A, Shaag A, Houtkooper RH, Hindi T, de Lonlay P, Erez G, Hubert L, Saada A, de Keyzer Y, Eshel G, Vaz FM, Pines O, Elpeleg O.

Am J Hum Genet. 2008 Oct;83(4):489-94. doi: 10.1016/j.ajhg.2008.09.002. Epub 2008 Sep 25. Erratum in: Am J Hum Genet. 2009 Jan;84(1):95.

PubMed [citation]

PMID:: 18817903
PMCID:: PMC2561931

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002249553.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change affects an acceptor splice site in intron 12 of the LPIN1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LPIN1 are known to be pathogenic (PMID: 18817903, 20583302, 22481384, 26111941). This variant is present in population databases (rs533651991, gnomAD 0.006%). Disruption of this splice site has been observed in individuals with clinical features of autosomal recessive myoglobinuria (PMID: 35242575; Invitae). ClinVar contains an entry for this variant (Variation ID: 1465375). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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

From Mayo Clinic Laboratories, Mayo Clinic, SCV004226539.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (2)

Description

PM2, PVS1

#	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		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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