NM_000302.4(PLOD1):c.1494C>G (p.Asn498Lys) AND Ehlers-Danlos syndrome, kyphoscoliotic type 1

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 1, 2021
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:: RCV001331146.6

Allele description [Variation Report for NM_000302.4(PLOD1):c.1494C>G (p.Asn498Lys)]

NM_000302.4(PLOD1):c.1494C>G (p.Asn498Lys)

Gene:

PLOD1:procollagen-lysine,2-oxoglutarate 5-dioxygenase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.22

Genomic location:

Preferred name:

NM_000302.4(PLOD1):c.1494C>G (p.Asn498Lys)

HGVS:

NC_000001.11:g.11965503C>G
NG_008159.1:g.35815C>G
NM_000302.4:c.1494C>GMANE SELECT
NM_001316320.2:c.1635C>G
NP_000293.2:p.Asn498Lys
NP_001303249.1:p.Asn545Lys
NC_000001.10:g.12025560C>G
NM_000302.3:c.1494C>G

Protein change:

N498K

Links:

dbSNP: rs1645810603

NCBI 1000 Genomes Browser:

rs1645810603

Molecular consequence:

NM_000302.4:c.1494C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001316320.2:c.1635C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Ehlers-Danlos syndrome, kyphoscoliotic type 1 (EDSKSCL1)
Synonyms:: EHLERS-DANLOS SYNDROME, TYPE VIA; EHLERS-DANLOS SYNDROME, OCULAR-SCOLIOTIC TYPE; Nevo syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0016002; MedGen: C0268342; Orphanet: 1900; OMIM: 225400

Recent activity

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Rattus norvegicus glia maturation factor, beta (Gmfb), mRNA
Rattus norvegicus glia maturation factor, beta (Gmfb), mRNA
gi|13624294|ref|NM_031032.1|

Nucleotide
PREDICTED: glutamate receptor 2.8-like isoform X2 [Cucumis melo]
PREDICTED: glutamate receptor 2.8-like isoform X2 [Cucumis melo]
gi|659089049|ref|XP_008445301.1|

Protein
Mus musculus mRNA for thrombospondin type 1 domain, complete cds
Mus musculus mRNA for thrombospondin type 1 domain, complete cds
gi|4519540|dbj|AB016768.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001523102	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 3, 2019)	maternal	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002297963	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2021)	germline	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

SCV001523102

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 3, 2019)

maternal

clinical testing

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

SCV002297963

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2021)

germline

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	maternal	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

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

Details of each submission

From Baylor Genetics, SCV001523102.1

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

Description

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002297963.2

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

Description

This sequence change replaces asparagine with lysine at codon 498 of the PLOD1 protein (p.Asn498Lys). The asparagine residue is highly conserved and there is a moderate physicochemical difference between asparagine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with PLOD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1029783). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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