NM_000302.4(PLOD1):c.579G>A (p.Arg193=) AND Ehlers-Danlos syndrome, kyphoscoliotic type 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 2, 2021
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:: RCV000555163.5

Allele description [Variation Report for NM_000302.4(PLOD1):c.579G>A (p.Arg193=)]

NM_000302.4(PLOD1):c.579G>A (p.Arg193=)

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.579G>A (p.Arg193=)

HGVS:

NC_000001.11:g.11952735G>A
NG_008159.1:g.23047G>A
NM_000302.4:c.579G>AMANE SELECT
NM_001316320.2:c.720G>A
NP_000293.2:p.Arg193=
NP_001303249.1:p.Arg240=
NC_000001.10:g.12012792G>A
NM_000302.3:c.579G>A

Links:

dbSNP: rs1553134266

NCBI 1000 Genomes Browser:

rs1553134266

Molecular consequence:

NM_000302.4:c.579G>A - synonymous variant - [Sequence Ontology: SO:0001819]
NM_001316320.2:c.720G>A - synonymous variant - [Sequence Ontology: SO:0001819]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000631729	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 2, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000631729

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 2, 2021)

germline

clinical testing

PubMed (3)
[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

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]

PMID:: 17576681
PMCID:: PMC1934990

Statistical features of human exons and their flanking regions.

Zhang MQ.

Hum Mol Genet. 1998 May;7(5):919-32.

PubMed [citation]

PMID:: 9536098

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000631729.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change affects codon 193 of the PLOD1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PLOD1 protein. This variant also falls at the last nucleotide of exon 5, which is part of the consensus splice site for this exon. 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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: Aug 5, 2023

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