NM_000249.4(MLH1):c.735C>G (p.Tyr245Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 13, 2017
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:: RCV000657736.1

Allele description [Variation Report for NM_000249.4(MLH1):c.735C>G (p.Tyr245Ter)]

NM_000249.4(MLH1):c.735C>G (p.Tyr245Ter)

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.735C>G (p.Tyr245Ter)

HGVS:

NC_000003.12:g.37014489C>G
NG_007109.2:g.26140C>G
NM_000249.4:c.735C>GMANE SELECT
NM_001167617.3:c.441C>G
NM_001167618.3:c.12C>G
NM_001167619.3:c.12C>G
NM_001258271.2:c.735C>G
NM_001258273.2:c.12C>G
NM_001258274.3:c.12C>G
NM_001354615.2:c.12C>G
NM_001354616.2:c.12C>G
NM_001354617.2:c.12C>G
NM_001354618.2:c.12C>G
NM_001354619.2:c.12C>G
NM_001354620.2:c.441C>G
NM_001354621.2:c.-140+2390C>G
NM_001354622.2:c.-195C>G
NM_001354623.2:c.-195C>G
NM_001354624.2:c.-92C>G
NM_001354625.2:c.-92C>G
NM_001354626.2:c.-92C>G
NM_001354627.2:c.-92C>G
NM_001354628.2:c.735C>G
NM_001354629.2:c.636C>G
NM_001354630.2:c.735C>G
NP_000240.1:p.Tyr245Ter
NP_000240.1:p.Tyr245Ter
NP_001161089.1:p.Tyr147Ter
NP_001161090.1:p.Tyr4Ter
NP_001161091.1:p.Tyr4Ter
NP_001245200.1:p.Tyr245Ter
NP_001245202.1:p.Tyr4Ter
NP_001245203.1:p.Tyr4Ter
NP_001341544.1:p.Tyr4Ter
NP_001341545.1:p.Tyr4Ter
NP_001341546.1:p.Tyr4Ter
NP_001341547.1:p.Tyr4Ter
NP_001341548.1:p.Tyr4Ter
NP_001341549.1:p.Tyr147Ter
NP_001341557.1:p.Tyr245Ter
NP_001341558.1:p.Tyr212Ter
NP_001341559.1:p.Tyr245Ter
LRG_216t1:c.735C>G
LRG_216:g.26140C>G
LRG_216p1:p.Tyr245Ter
NC_000003.11:g.37055980C>G
NM_000249.3:c.735C>G

Protein change:

Y147*

Links:

dbSNP: rs1553645226

NCBI 1000 Genomes Browser:

rs1553645226

Molecular consequence:

NM_001354622.2:c.-195C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-195C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-92C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-92C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-92C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-92C>G - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-140+2390C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000249.4:c.735C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001167617.3:c.441C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001167618.3:c.12C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001167619.3:c.12C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001258271.2:c.735C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001258273.2:c.12C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001258274.3:c.12C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354615.2:c.12C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354616.2:c.12C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354617.2:c.12C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354618.2:c.12C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354619.2:c.12C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354620.2:c.441C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354628.2:c.735C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354629.2:c.636C>G - nonsense - [Sequence Ontology: SO:0001587]
NM_001354630.2:c.735C>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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beta-galactosidase [Enterobacter chengduensis]
beta-galactosidase [Enterobacter chengduensis]
gi|1733470902|gnl|PRJNA415108|FY206 0|gb|QEL35602.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000779486	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Sep 13, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000779486

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Sep 13, 2017)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000779486.2

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

Description

This variant is denoted MLH1 c.735C>G at the cDNA level and p.Tyr245Ter (Y245X) at the protein level. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAC>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.

#	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

Last Updated: Dec 30, 2023

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