NM_001844.5(COL2A1):c.3505G>A (p.Val1169Ile) AND Stickler syndrome type 1

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jul 1, 2022
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:: RCV001109931.6

Allele description [Variation Report for NM_001844.5(COL2A1):c.3505G>A (p.Val1169Ile)]

NM_001844.5(COL2A1):c.3505G>A (p.Val1169Ile)

Gene:

COL2A1:collagen type II alpha 1 chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q13.11

Genomic location:

Preferred name:

NM_001844.5(COL2A1):c.3505G>A (p.Val1169Ile)

HGVS:

NC_000012.12:g.47976055C>T
NG_008072.1:g.33448G>A
NM_001844.5:c.3505G>AMANE SELECT
NM_033150.3:c.3298G>A
NP_001835.3:p.Val1169Ile
NP_149162.2:p.Val1100Ile
NC_000012.11:g.48369838C>T
NM_001844.4:c.3505G>A

Protein change:

V1100I

Links:

dbSNP: rs760390497

NCBI 1000 Genomes Browser:

rs760390497

Molecular consequence:

NM_001844.5:c.3505G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033150.3:c.3298G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Stickler syndrome type 1 (STL1)
Synonyms:: Stickler syndrome, vitreous type 1; Stickler syndrome, membranous vitreous type; Arthroophthalmopathy, hereditary progressive
Identifiers:: MONDO: MONDO:0007160; MedGen: C2020284; Orphanet: 828; OMIM: 108300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001267315	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Jan 12, 2018)	germline	clinical testing	Citation Link,
SCV002576565	Center of Medical Genetics, Central South University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 1, 2022)	inherited, not applicable	research, in vitro	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001267315

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Jan 12, 2018)

germline

clinical testing

Citation Link,

SCV002576565

Center of Medical Genetics, Central South University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jul 1, 2022)

inherited, not applicable

research, in vitro

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	inherited	yes	6	1	not provided	not provided	yes	research
not provided	not applicable	not applicable	not provided	not provided	not provided	not provided	not provided	in vitro
not provided	germline	unknown	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 Illumina Laboratory Services, Illumina, SCV001267315.1

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#	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 Center of Medical Genetics, Central South University, SCV002576565.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	6	not provided	yes	research	PubMed (1)
2	not provided	not provided	not provided	not provided	in vitro	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	inherited	yes	not provided	not provided	not provided		6	not provided	1	not provided
2	not applicable	not applicable	not provided	not provided	assert pathogenicity		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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