NM_000306.4(POU1F1):c.747del (p.Glu250fs) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 26, 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:: RCV003556018.2

Allele description [Variation Report for NM_000306.4(POU1F1):c.747del (p.Glu250fs)]

NM_000306.4(POU1F1):c.747del (p.Glu250fs)

Gene:

POU1F1:POU class 1 homeobox 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p11.2

Genomic location:

Preferred name:

NM_000306.4(POU1F1):c.747del (p.Glu250fs)

HGVS:

NC_000003.12:g.87260024del
NG_008225.2:g.21565del
NM_000306.4:c.747delMANE SELECT
NM_001122757.3:c.825del
NP_000297.1:p.Glu250fs
NP_001116229.1:p.Glu276fs
NC_000003.11:g.87309173del
NC_000003.11:g.87309174del
NM_000306.3:c.747del

Protein change:

E250fs

Links:

OMIM: 173110.0009; dbSNP: rs587776798

NCBI 1000 Genomes Browser:

rs587776798

Molecular consequence:

NM_000306.4:c.747del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001122757.3:c.825del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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zinc finger C2HC domain-containing protein 1A isoform 1 [Mus musculus]
zinc finger C2HC domain-containing protein 1A isoform 1 [Mus musculus]
gi|27502351|ref|NP_775273.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004293117	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 26, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 32894409, 11297581, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004293117

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 26, 2022)

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

Genetic spectrum and predictors of mutations in four known genes in Asian Indian patients with growth hormone deficiency and orthotopic posterior pituitary: an emphasis on regional genetic diversity.

Kale S, Gada JV, Jadhav S, Lila AR, Sarathi V, Budyal S, Patt H, Goroshi MR, Thadani PM, Arya S, Kamble AA, Patil VA, Acharya S, Sankhe S, Shivane V, Raghavan V, Bandgar TR, Shah NS.

Pituitary. 2020 Dec;23(6):701-715. doi: 10.1007/s11102-020-01078-4.

PubMed [citation]

PMID:: 32894409

Combined pituitary hormone deficiency caused by compound heterozygosity for two novel mutations in the POU domain of the Pit1/POU1F1 gene.

Hendriks-Stegeman BI, Augustijn KD, Bakker B, Holthuizen P, van der Vliet PC, Jansen M.

J Clin Endocrinol Metab. 2001 Apr;86(4):1545-50.

PubMed [citation]

PMID:: 11297581

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004293117.1

#	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. This variant disrupts a region of the POU1F1 protein in which other variant(s) (p.E250*) have been observed in individuals with POU1F1-related conditions (PMID: 32894409). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Experimental studies have shown that this premature translational stop signal affects POU1F1 function (PMID: 11297581). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 13610). This premature translational stop signal has been observed in individual(s) with POU1F1-related conditions (PMID: 11297581). This variant is present in population databases (rs587776798, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Glu250Asnfs*2) in the POU1F1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the POU1F1 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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