NM_000249.4(MLH1):c.622C>T (p.Pro208Ser) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 22, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000212523.21

Allele description [Variation Report for NM_000249.4(MLH1):c.622C>T (p.Pro208Ser)]

NM_000249.4(MLH1):c.622C>T (p.Pro208Ser)

Gene:

MLH1:mutL homolog 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.622C>T (p.Pro208Ser)

Other names:

p.P208S:CCC>TCC

HGVS:

NC_000003.12:g.37012044C>T
NG_007109.2:g.23695C>T
NM_000249.4:c.622C>TMANE SELECT
NM_001167617.3:c.328C>T
NM_001167618.3:c.-102C>T
NM_001167619.3:c.-102C>T
NM_001258271.2:c.622C>T
NM_001258273.2:c.-102C>T
NM_001258274.3:c.-102C>T
NM_001354615.2:c.-102C>T
NM_001354616.2:c.-102C>T
NM_001354617.2:c.-102C>T
NM_001354618.2:c.-102C>T
NM_001354619.2:c.-102C>T
NM_001354620.2:c.328C>T
NM_001354621.2:c.-195C>T
NM_001354622.2:c.-308C>T
NM_001354623.2:c.-308C>T
NM_001354624.2:c.-205C>T
NM_001354625.2:c.-205C>T
NM_001354626.2:c.-205C>T
NM_001354627.2:c.-205C>T
NM_001354628.2:c.622C>T
NM_001354629.2:c.523C>T
NM_001354630.2:c.622C>T
NP_000240.1:p.Pro208Ser
NP_000240.1:p.Pro208Ser
NP_001161089.1:p.Pro110Ser
NP_001245200.1:p.Pro208Ser
NP_001341549.1:p.Pro110Ser
NP_001341557.1:p.Pro208Ser
NP_001341558.1:p.Pro175Ser
NP_001341559.1:p.Pro208Ser
LRG_216t1:c.622C>T
LRG_216:g.23695C>T
LRG_216p1:p.Pro208Ser
NC_000003.11:g.37053535C>T
NM_000249.3:c.622C>T
p.P208S

Protein change:

P110S

Links:

dbSNP: rs587781509

NCBI 1000 Genomes Browser:

rs587781509

Molecular consequence:

NM_001167618.3:c.-102C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-102C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-102C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-102C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-102C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-102C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-102C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-102C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-102C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-195C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-308C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-308C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-205C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-205C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-205C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-205C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.622C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001167617.3:c.328C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001258271.2:c.622C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354620.2:c.328C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.622C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354629.2:c.523C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.622C>T - 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
SCV000211094	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jan 22, 2024)	germline	clinical testing	Citation Link,
SCV002009355	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 3, 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

SCV000211094

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jan 22, 2024)

germline

clinical testing

Citation Link,

SCV002009355

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 3, 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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From GeneDx, SCV000211094.13

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in cases and controls in a breast cancer study (PMID: 28157215); This variant is associated with the following publications: (PMID: 22753075, 33471991, 28157215)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV002009355.3

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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