NM_006261.5(PROP1):c.386_387dup (p.Ser130fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 24, 2021
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:: RCV001388459.7

Allele description [Variation Report for NM_006261.5(PROP1):c.386_387dup (p.Ser130fs)]

NM_006261.5(PROP1):c.386_387dup (p.Ser130fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

5q35.3

Genomic location:

Preferred name:

NM_006261.5(PROP1):c.386_387dup (p.Ser130fs)

HGVS:

NC_000005.10:g.177993003GC[3]
NG_015889.1:g.8237GC[3]
NM_006261.5:c.386_387dupMANE SELECT
NP_006252.4:p.Ser130fs
NC_000005.9:g.177420003_177420004insGC
NC_000005.9:g.177420004GC[3]

Protein change:

S130fs

Links:

dbSNP: rs1554182405

NCBI 1000 Genomes Browser:

rs1554182405

Molecular consequence:

NM_006261.5:c.386_387dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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CLDN5 [Dasypus novemcinctus]
CLDN5 [Dasypus novemcinctus]
Gene ID:101414272

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ERLEC1 [Vicugna pacos]
Gene ID:102537583

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001589458	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 24, 2021)	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

SCV001589458

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 24, 2021)

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 Invitae, SCV001589458.5

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

Description

This variant has not been reported in the literature in individuals with PROP1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the PROP1 gene (p.Ser130Alafs*36). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 97 amino acids of the PROP1 protein. This variant disrupts the C-terminus of the PROP1 protein. Other variant(s) that disrupt this region (p.Trp194*) have been determined to be pathogenic (PMID: 15941866, 20381582, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

#	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: Jun 17, 2024

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