NM_005022.4(PFN1):c.341T>C (p.Met114Thr) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 11, 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:: RCV001852610.3

Allele description [Variation Report for NM_005022.4(PFN1):c.341T>C (p.Met114Thr)]

NM_005022.4(PFN1):c.341T>C (p.Met114Thr)

Gene:

PFN1:profilin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.2

Genomic location:

Preferred name:

NM_005022.4(PFN1):c.341T>C (p.Met114Thr)

HGVS:

NC_000017.11:g.4945982A>G
NG_012063.2:g.4892A>G
NG_032945.1:g.8105T>C
NM_001375991.1:c.*425T>C
NM_005022.4:c.341T>CMANE SELECT
NP_005013.1:p.Met114Thr
NC_000017.10:g.4849277A>G
P07737:p.Met114Thr

Protein change:

M114T; MET114THR

Links:

UniProtKB: P07737#VAR_068926; OMIM: 176610.0002; dbSNP: rs387907265

NCBI 1000 Genomes Browser:

rs387907265

Molecular consequence:

NM_001375991.1:c.*425T>C - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_005022.4:c.341T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002235995	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 11, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22801503, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002235995

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 11, 2021)

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

Mutations in the profilin 1 gene cause familial amyotrophic lateral sclerosis.

Wu CH, Fallini C, Ticozzi N, Keagle PJ, Sapp PC, Piotrowska K, Lowe P, Koppers M, McKenna-Yasek D, Baron DM, Kost JE, Gonzalez-Perez P, Fox AD, Adams J, Taroni F, Tiloca C, Leclerc AL, Chafe SC, Mangroo D, Moore MJ, Zitzewitz JA, Xu ZS, et al.

Nature. 2012 Aug 23;488(7412):499-503. doi: 10.1038/nature11280.

PubMed [citation]

PMID:: 22801503
PMCID:: PMC3575525

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002235995.3

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

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PFN1 function (PMID: 22801503). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 37035). This missense change has been observed in individual(s) with amyotrophic lateral sclerosis (PMID: 22801503). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 114 of the PFN1 protein (p.Met114Thr).

#	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 14, 2024

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