NM_018670.4(MESP1):c.139C>G (p.Pro47Ala) AND Congenital heart disease

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 2, 2022
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:: RCV002273028.2

Allele description [Variation Report for NM_018670.4(MESP1):c.139C>G (p.Pro47Ala)]

NM_018670.4(MESP1):c.139C>G (p.Pro47Ala)

Genes:

LOC130057889:ATAC-STARR-seq lymphoblastoid silent region 6804 [Gene]
MESP1:mesoderm posterior bHLH transcription factor 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q26.1

Genomic location:

Preferred name:

NM_018670.4(MESP1):c.139C>G (p.Pro47Ala)

HGVS:

NC_000015.10:g.89751093G>C
NM_018670.4:c.139C>GMANE SELECT
NP_061140.1:p.Pro47Ala
NC_000015.9:g.90294324G>C
NM_018670.3:c.139C>G

Protein change:

P47A

Links:

dbSNP: rs933736116

NCBI 1000 Genomes Browser:

rs933736116

Molecular consequence:

NM_018670.4:c.139C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital heart disease (CHD)
Identifiers:: MONDO: MONDO:0005453; MedGen: C0152021

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002557582	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 2, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24056064, 26694203, 28677747, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002557582

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 2, 2022)

germline

clinical testing

PubMed (4)
[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

Mutational analysis of the human MESP1 gene in patients with congenital heart disease reveals a highly variable sequence in exon 1.

Lahm H, Deutsch MA, Dreßen M, Doppler S, Werner A, Hörer J, Cleuziou J, Schreiber C, Böhm J, Laugwitz KL, Lange R, Krane M.

Eur J Med Genet. 2013 Nov;56(11):591-8. doi: 10.1016/j.ejmg.2013.09.001. Epub 2013 Sep 19.

PubMed [citation]

PMID:: 24056064

MESP1 Mutations in Patients with Congenital Heart Defects.

Werner P, Latney B, Deardorff MA, Goldmuntz E.

Hum Mutat. 2016 Mar;37(3):308-14. doi: 10.1002/humu.22947. Epub 2016 Jan 19.

PubMed [citation]

PMID:: 26694203
PMCID:: PMC4762608

See all PubMed Citations (4)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002557582.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3C. Following criteria are met: 0102 - Loss of function is a mechanism of disease in this gene and is associated with congenital heart defects (PMIDs: 26694203, 28677747). While loss of function has been demonstrated for null variants, the mechanism for missense variants in currently unclear (PMIDs: 24056064, 26694203). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to alanine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (2 heterozygotes, 0 homozygotes). (SP) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools or not conserved in placental mammals with a minor amino acid change. (SB) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1207 - Parental origin of the variant is unresolved. The proband's father has not been tested for the variant and it is therefore unknown if the variant is paternally inherited or de novo. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#	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: Feb 28, 2024

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