NM_001130144.3(LTBP3):c.3676G>A (p.Gly1226Ser) AND Brachyolmia-amelogenesis imperfecta syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 31, 2023
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:: RCV001885537.5

Allele description [Variation Report for NM_001130144.3(LTBP3):c.3676G>A (p.Gly1226Ser)]

NM_001130144.3(LTBP3):c.3676G>A (p.Gly1226Ser)

Gene:

LTBP3:latent transforming growth factor beta binding protein 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q13.1

Genomic location:

Preferred name:

NM_001130144.3(LTBP3):c.3676G>A (p.Gly1226Ser)

HGVS:

NC_000011.10:g.65539412C>T
NG_016437.1:g.23817G>A
NG_047172.1:g.19348C>T
NM_001130144.2:c.3676G>A
NM_001130144.3:c.3676G>AMANE SELECT
NM_001164266.1:c.3184G>A
NM_021070.4:c.3535G>A
NP_001123616.1:p.Gly1226Ser
NP_001157738.1:p.Gly1062Ser
NP_066548.2:p.Gly1179Ser
NC_000011.9:g.65306883C>T

Protein change:

G1062S

Links:

dbSNP: rs1445499882

NCBI 1000 Genomes Browser:

rs1445499882

Molecular consequence:

NM_001130144.3:c.3676G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001164266.1:c.3184G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_021070.4:c.3535G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Brachyolmia-amelogenesis imperfecta syndrome
Synonyms:: PLATYSPONDYLY WITH AMELOGENESIS IMPERFECTA; Tooth agenesis, selective, 6; Dental anomalies and short stature
Identifiers:: MONDO: MONDO:0011018; MedGen: C1832594; Orphanet: 2899; OMIM: 601216

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002113374	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 31, 2023)	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

SCV002113374

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 31, 2023)

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

Citations

PubMed

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002113374.4

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

Description

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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 1353486). This variant has not been reported in the literature in individuals affected with LTBP3-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1226 of the LTBP3 protein (p.Gly1226Ser).

#	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: May 16, 2025

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