NM_001349206.2(LPIN1):c.854C>A (p.Thr285Lys) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: May 16, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV001759892.10

Allele description [Variation Report for NM_001349206.2(LPIN1):c.854C>A (p.Thr285Lys)]

NM_001349206.2(LPIN1):c.854C>A (p.Thr285Lys)

Genes:

LOC126806147:CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:11919054-11920253 [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.854C>A (p.Thr285Lys)

Other names:

p.Thr249Lys

HGVS:

NC_000002.12:g.11779542C>A
NG_012843.2:g.106964C>A
NM_001261427.3:c.764C>A
NM_001261428.3:c.1001C>A
NM_001349199.2:c.746C>A
NM_001349200.2:c.746C>A
NM_001349201.2:c.746C>A
NM_001349202.2:c.851C>A
NM_001349203.2:c.851C>A
NM_001349204.2:c.854C>A
NM_001349205.2:c.854C>A
NM_001349206.2:c.854C>AMANE SELECT
NM_001349207.2:c.944C>A
NM_001349208.2:c.893C>A
NM_145693.4:c.746C>A
NP_001248356.1:p.Thr255Lys
NP_001248357.1:p.Thr334Lys
NP_001336128.1:p.Thr249Lys
NP_001336129.1:p.Thr249Lys
NP_001336130.1:p.Thr249Lys
NP_001336131.1:p.Thr284Lys
NP_001336132.1:p.Thr284Lys
NP_001336133.1:p.Thr285Lys
NP_001336134.1:p.Thr285Lys
NP_001336135.1:p.Thr285Lys
NP_001336136.1:p.Thr315Lys
NP_001336137.1:p.Thr298Lys
NP_663731.1:p.Thr249Lys
NC_000002.11:g.11919668C>A
NC_000002.11:g.11919668C>A
NM_145693.2:c.746C>A
NR_146080.2:n.795C>A

Protein change:

T249K

Links:

dbSNP: rs141555457

NCBI 1000 Genomes Browser:

rs141555457

Molecular consequence:

NM_001261427.3:c.764C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001261428.3:c.1001C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349199.2:c.746C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349200.2:c.746C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349201.2:c.746C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349202.2:c.851C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349203.2:c.851C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349204.2:c.854C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349205.2:c.854C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349206.2:c.854C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349207.2:c.944C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001349208.2:c.893C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_145693.4:c.746C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_146080.2:n.795C>A - 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
SCV001995937	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Sep 25, 2019)	germline	clinical testing	Citation Link,
SCV002459644	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 26, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005411618	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 16, 2024)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 31617323, 32041611, 35460704, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001995937

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Sep 25, 2019)

germline

clinical testing

Citation Link,

SCV002459644

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 26, 2024)

germline

clinical testing

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

SCV005411618

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(May 16, 2024)

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	2	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	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

Three patients with homozygous familial hypercholesterolemia: Genomic sequencing and kindred analysis.

Wong KHY, Levy-Sakin M, Ma W, Gonzaludo N, Mak ACY, Vaka D, Poon A, Chu C, Lao R, Balamir M, Grenville Z, Wong N, Kane JP, Kwok PY, Malloy MJ, Pullinger CR.

Mol Genet Genomic Med. 2019 Dec;7(12):e1007. doi: 10.1002/mgg3.1007. Epub 2019 Oct 16.

PubMed [citation]

PMID:: 31617323
PMCID:: PMC6900368

See all PubMed Citations (5)

Details of each submission

From GeneDx, SCV001995937.2

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

Description

In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32041611)

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002459644.3

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

#	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, SCV005411618.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (4)

Description

BS1

#	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		2	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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