NM_006261.5(PROP1):c.581G>A (p.Trp194Ter) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 25, 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:: RCV003566568.2

Allele description [Variation Report for NM_006261.5(PROP1):c.581G>A (p.Trp194Ter)]

NM_006261.5(PROP1):c.581G>A (p.Trp194Ter)

Gene:

PROP1:PROP paired-like homeobox 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q35.3

Genomic location:

Preferred name:

NM_006261.5(PROP1):c.581G>A (p.Trp194Ter)

HGVS:

NC_000005.10:g.177992809C>T
NG_015889.1:g.8434G>A
NG_015889.2:g.8433G>A
NM_006261.5:c.581G>AMANE SELECT
NP_006252.4:p.Trp194Ter
NC_000005.9:g.177419810C>T

Protein change:

W194*

Molecular consequence:

NM_006261.5:c.581G>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV004317871	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 25, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15941866, 20381582, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004317871

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 25, 2023)

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

An uncommon phenotype with familial central hypogonadism caused by a novel PROP1 gene mutant truncated in the transactivation domain.

Reynaud R, Barlier A, Vallette-Kasic S, Saveanu A, Guillet MP, Simonin G, Enjalbert A, Valensi P, Brue T.

J Clin Endocrinol Metab. 2005 Aug;90(8):4880-7. Epub 2005 Jun 7.

PubMed [citation]

PMID:: 15941866

W194XProp1 and S156insTProp1, both of which have intact DNA-binding domain, show a different DNA-binding activity to the Prop1-binding element in human Pit-1 gene.

Shibahara H, Ikeshita N, Sugiyama Y, Toda K, Yamamoto D, Herningtyas EH, Maki T, Kubota E, Iguchi G, Iida K, Takahashi Y, Kaji H, Chihara K, Okimura Y.

Mol Cell Endocrinol. 2010 Jul 29;323(2):167-71. doi: 10.1016/j.mce.2010.03.023. Epub 2010 Apr 8.

PubMed [citation]

PMID:: 20381582

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004317871.1

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. A different variant (c.582G>A ) giving rise to the same protein effect has been determined to be pathogenic (PMID: 15941866, 20381582). This suggests that this variant is also likely to be causative of disease. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp194*) in the PROP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 33 amino acid(s) of the PROP1 protein.

#	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: Sep 29, 2024

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