NM_178172.6(GPIHBP1):c.320C>G (p.Ser107Cys) AND Hyperlipoproteinemia, type 1D

Germline classification:: Likely pathogenic (3 submissions)
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:: RCV000133530.17

Allele description [Variation Report for NM_178172.6(GPIHBP1):c.320C>G (p.Ser107Cys)]

NM_178172.6(GPIHBP1):c.320C>G (p.Ser107Cys)

Gene:

GPIHBP1:glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q24.3

Genomic location:

Preferred name:

NM_178172.6(GPIHBP1):c.320C>G (p.Ser107Cys)

HGVS:

NC_000008.11:g.143215283C>G
NG_034256.1:g.7091C>G
NM_001301772.2:c.320C>G
NM_178172.6:c.320C>GMANE SELECT
NP_001288701.1:p.Ser107Cys
NP_835466.2:p.Ser107Cys
NP_835466.2:p.Ser107Cys
NP_835466.2:p.Ser107Cys
NC_000008.10:g.144297158C>G
NM_178172.5:c.320C>G

Protein change:

S107C; SER107CYS

Links:

OMIM: 612757.0010; dbSNP: rs587777643

NCBI 1000 Genomes Browser:

rs587777643

Molecular consequence:

NM_001301772.2:c.320C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_178172.6:c.320C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hyperlipoproteinemia, type 1D
Synonyms:: Hyperlipoproteinemia, type ID
Identifiers:: MONDO: MONDO:0014412; MedGen: C4014767; Orphanet: 444490; OMIM: 615947

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000188605	OMIM	no assertion criteria provided	Pathogenic (Jul 11, 2014)	germline	literature only	Plengpanich, W., Young, S. G., Khovidhunkit, W., Bensadoun, A., Karnman, H., Ploug, M., Gardsvoll, H., Leung, C. S., Adeyo, O., Larsson, M., Muanpetch, S., Charoen, S., Fong, L. G., Niramitmahapanya, S., Beigneux, A. P. Multimerization of glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) and familial chylomicronemia from a serine-to-cysteine substitution in GPIHBP1 Ly6 domain. J. Biol. Chem. 289: 19491-19499, 2014.,
SCV004047658	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005061771	Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	biparental	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

SCV000188605

OMIM

no assertion criteria provided

Pathogenic
(Jul 11, 2014)

germline

literature only

Plengpanich, W., Young, S. G., Khovidhunkit, W., Bensadoun, A., Karnman, H., Ploug, M., Gardsvoll, H., Leung, C. S., Adeyo, O., Larsson, M., Muanpetch, S., Charoen, S., Fong, L. G., Niramitmahapanya, S., Beigneux, A. P. Multimerization of glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) and familial chylomicronemia from a serine-to-cysteine substitution in GPIHBP1 Ly6 domain. J. Biol. Chem. 289: 19491-19499, 2014.,

SCV004047658

Neuberg Centre For Genomic Medicine, NCGM

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

germline

clinical testing

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

SCV005061771

Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

biparental

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	biparental	yes	1	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000188605.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	not provided

Description

In 3 sibs with severe hypertriglyceridemia (615947), Plengpanich et al. (2014) identified homozygosity for a 320C-G transversion in the GPIHPB1 gene, resulting in a ser107-to-cys (S107C) substitution in the Ly6 domain of the protein. The mutation resulted in a gain of function and multimerization of GPIHBP1, precluding LPL binding. Hamosh (2014) noted that the S107C mutation was not present in the Exome Variant Server database.

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

From Neuberg Centre For Genomic Medicine, NCGM, SCV004047658.1

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

Description

The missense variant c.320C>G (p.Ser107Cys) in GPIHBP1 gene has previously been reported in homozygous state in patients affected with hypertriglyceridemia (Plengpanich W. et al.,2014). The p.Ser107Cys variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.0008016% is reported in gnomAD. This variant has been reported to the ClinVar database as Pathogenic but no details are available for independent assessment. The amino acid Ser at position 107 is changed to a Cys changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Ser107Cys in GPIHBP1 is predicted as conserved by GERP++. For these reasons, this variant has been classified as Likely Pathogenic.

#	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 Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India, SCV005061771.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		1	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	biparental	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Dec 7, 2024

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