NM_000088.4(COL1A1):c.436C>A (p.Pro146Thr) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jun 22, 2024
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:: RCV000788756.7

Allele description [Variation Report for NM_000088.4(COL1A1):c.436C>A (p.Pro146Thr)]

NM_000088.4(COL1A1):c.436C>A (p.Pro146Thr)

Gene:

COL1A1:collagen type I alpha 1 chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.33

Genomic location:

Preferred name:

NM_000088.4(COL1A1):c.436C>A (p.Pro146Thr)

HGVS:

NC_000017.11:g.50199261G>T
NG_007400.1:g.7379C>A
NM_000088.4:c.436C>AMANE SELECT
NP_000079.2:p.Pro146Thr
NP_000079.2:p.Pro146Thr
LRG_1t1:c.436C>A
LRG_1:g.7379C>A
LRG_1p1:p.Pro146Thr
NC_000017.10:g.48276622G>T
NM_000088.3:c.436C>A

Protein change:

P146T

Links:

dbSNP: rs756846639

NCBI 1000 Genomes Browser:

rs756846639

Molecular consequence:

NM_000088.4:c.436C>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000927989	Blueprint Genetics	criteria provided, single submitter (Blueprint Genetics Variant Classification Scheme)	Uncertain significance (Oct 14, 2018)	germline	clinical testing	Citation Link,
SCV001826198	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jun 22, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000927989

Blueprint Genetics

criteria provided, single submitter

(Blueprint Genetics Variant Classification Scheme)

Uncertain significance
(Oct 14, 2018)

germline

clinical testing

Citation Link,

SCV001826198

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jun 22, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Blueprint Genetics, SCV000927989.1

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

#	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 GeneDx, SCV001826198.4

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

Description

Reported in a patient with osteogenesis imperfecta; of note, this patient also harbored a COL1A1 pathogenic variant (PMID: 18996919); Observed in a patient with the diagnosis of classical EDS; however, no additional phenotypic or segregation data were available for review (PMID: 28748566); Reported in two individuals with bleeding diathesis and hypermobility (PMID: 33161638); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur (HGMD); This variant is associated with the following publications: (PMID: 33161638, 18996919, 28748566)

#	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

Last Updated: Sep 29, 2024

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