NM_015450.3(POT1):c.925T>C (p.Ser309Pro) AND Tumor predisposition syndrome 3

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 30, 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:: RCV000798492.9

Allele description [Variation Report for NM_015450.3(POT1):c.925T>C (p.Ser309Pro)]

NM_015450.3(POT1):c.925T>C (p.Ser309Pro)

Gene:

POT1:protection of telomeres 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q31.33

Genomic location:

Preferred name:

NM_015450.3(POT1):c.925T>C (p.Ser309Pro)

HGVS:

NC_000007.14:g.124851896A>G
NG_029232.1:g.83088T>C
NM_001042594.2:c.532T>C
NM_015450.3:c.925T>CMANE SELECT
NP_001036059.1:p.Ser178Pro
NP_056265.2:p.Ser309Pro
NC_000007.13:g.124491950A>G
NM_015450.2:c.925T>C
NR_003102.2:n.1368T>C
NR_003103.2:n.1368T>C
NR_003104.2:n.1368T>C

Protein change:

S178P

Links:

dbSNP: rs1584764901

NCBI 1000 Genomes Browser:

rs1584764901

Molecular consequence:

NM_001042594.2:c.532T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_015450.3:c.925T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_003102.2:n.1368T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_003103.2:n.1368T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_003104.2:n.1368T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Tumor predisposition syndrome 3 (TPDS3)
Synonyms:: Melanoma, cutaneous malignant, susceptibility to, 10; LONG TELOMERE SYNDROME, POT1-RELATED; Glioma susceptibility 9
Identifiers:: MONDO: MONDO:0014368; MedGen: C4014476; Orphanet: 618; OMIM: 615848

Recent activity

Clear Turn Off Turn On

Influenza A virus (A/New York/713/1994(H3N2)) segment 6, complete sequence
Influenza A virus (A/New York/713/1994(H3N2)) segment 6, complete sequence
gi|110629264|gnl|NIGSP|NIGSP-NYS-00 A|gb|CY012554.1|

Nucleotide
Anatomy, Head and Neck: Carotid Baroreceptors - StatPearls
Anatomy, Head and Neck: Carotid Baroreceptors - StatPearls
cn04e07.y1 Normal Human Trabecular Bone Cells Homo sapiens cDNA clone NHTBC_cn04...
cn04e07.y1 Normal Human Trabecular Bone Cells Homo sapiens cDNA clone NHTBC_cn04e07 random, mRNA sequence
gi|5128896|gnl|dbEST|2660378|gb|AI7 .1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000938111	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 30, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000938111

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 30, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

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 Invitae, SCV000938111.6

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

Description

This variant has not been reported in the literature in individuals with POT1-related disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with proline at codon 309 of the POT1 protein (p.Ser309Pro). The serine residue is moderately conserved and there is a moderate physicochemical difference between serine and proline.

#	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

ClinVar

Relating variation to medicine