NM_000535.7(PMS2):c.1673C>T (p.Thr558Ile) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 10, 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:: RCV000165670.4

Allele description [Variation Report for NM_000535.7(PMS2):c.1673C>T (p.Thr558Ile)]

NM_000535.7(PMS2):c.1673C>T (p.Thr558Ile)

Gene:

PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p22.1

Genomic location:

Preferred name:

NM_000535.7(PMS2):c.1673C>T (p.Thr558Ile)

HGVS:

NC_000007.14:g.5987092G>A
NG_008466.1:g.27015C>T
NM_000535.7:c.1673C>TMANE SELECT
NM_001322003.2:c.1268C>T
NM_001322004.2:c.1268C>T
NM_001322005.2:c.1268C>T
NM_001322006.2:c.1517C>T
NM_001322007.2:c.1355C>T
NM_001322008.2:c.1355C>T
NM_001322009.2:c.1268C>T
NM_001322010.2:c.1112C>T
NM_001322011.2:c.740C>T
NM_001322012.2:c.740C>T
NM_001322013.2:c.1100C>T
NM_001322014.2:c.1673C>T
NM_001322015.2:c.1364C>T
NP_000526.2:p.Thr558Ile
NP_001308932.1:p.Thr423Ile
NP_001308933.1:p.Thr423Ile
NP_001308934.1:p.Thr423Ile
NP_001308935.1:p.Thr506Ile
NP_001308936.1:p.Thr452Ile
NP_001308937.1:p.Thr452Ile
NP_001308938.1:p.Thr423Ile
NP_001308939.1:p.Thr371Ile
NP_001308940.1:p.Thr247Ile
NP_001308941.1:p.Thr247Ile
NP_001308942.1:p.Thr367Ile
NP_001308943.1:p.Thr558Ile
NP_001308944.1:p.Thr455Ile
LRG_161t1:c.1673C>T
LRG_161:g.27015C>T
NC_000007.13:g.6026723G>A
NM_000535.5:c.1673C>T
NM_000535.6:c.1673C>T
NR_136154.1:n.1760C>T
p.T558I

Protein change:

T247I

Links:

dbSNP: rs114037612

NCBI 1000 Genomes Browser:

rs114037612

Molecular consequence:

NM_000535.7:c.1673C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.1268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.1268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.1268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.1517C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.1355C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.1355C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.1268C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.1112C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322011.2:c.740C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322012.2:c.740C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322013.2:c.1100C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.1673C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.1364C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.1760C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000216408	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Aug 10, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000216408

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Aug 10, 2023)

germline

clinical testing

Citation Link

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

Details of each submission

From Ambry Genetics, SCV000216408.7

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

Description

The p.T558I variant (also known as c.1673C>T), located in coding exon 11 of the PMS2 gene, results from a C to T substitution at nucleotide position 1673. The threonine at codon 558 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Mar 5, 2024

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