NM_006261.5(PROP1):c.63del (p.Leu22fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 15, 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:: RCV001383228.7

Allele description [Variation Report for NM_006261.5(PROP1):c.63del (p.Leu22fs)]

NM_006261.5(PROP1):c.63del (p.Leu22fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

5q35.3

Genomic location:

Preferred name:

NM_006261.5(PROP1):c.63del (p.Leu22fs)

HGVS:

NC_000005.10:g.177995871del
NG_015889.1:g.5372del
NM_006261.5:c.63delMANE SELECT
NP_006252.4:p.Leu22fs
NC_000005.9:g.177422872del

Protein change:

L22fs

Links:

dbSNP: rs780134343

NCBI 1000 Genomes Browser:

rs780134343

Molecular consequence:

NM_006261.5:c.63del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001582315	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 15, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33270637, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001582315

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 15, 2023)

germline

clinical testing

PubMed (2)
[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

Pituitary stalk interruption syndrome is characterized by genetic heterogeneity.

Brauner R, Bignon-Topalovic J, Bashamboo A, McElreavey K.

PLoS One. 2020;15(12):e0242358. doi: 10.1371/journal.pone.0242358.

PubMed [citation]

PMID:: 33270637
PMCID:: PMC7714207

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, SCV001582315.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Leu22Cysfs*143) in the PROP1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 205 amino acid(s) of the PROP1 protein. This variant is present in population databases (rs780134343, gnomAD 0.007%). This premature translational stop signal has been observed in individual(s) with clinical features of PROP1-related conditions (PMID: 33270637). ClinVar contains an entry for this variant (Variation ID: 1070901). This variant disrupts a region of the PROP1 protein in which other variant(s) (p.Trp194*) have been determined to be pathogenic (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. 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: Sep 29, 2024

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