NM_000249.4(MLH1):c.43G>A (p.Val15Met) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely benign (1 submission)
Last evaluated:: Dec 16, 2020
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:: RCV000221816.4

Allele description [Variation Report for NM_000249.4(MLH1):c.43G>A (p.Val15Met)]

NM_000249.4(MLH1):c.43G>A (p.Val15Met)

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.43G>A (p.Val15Met)

HGVS:

NC_000003.12:g.36993590G>A
NG_007109.2:g.5241G>A
NG_008418.1:g.4715C>T
NM_000249.4:c.43G>AMANE SELECT
NM_001167617.3:c.-474G>A
NM_001167618.3:c.-903G>A
NM_001167619.3:c.-816G>A
NM_001258271.2:c.43G>A
NM_001258273.2:c.-590G>A
NM_001258274.3:c.-1053G>A
NM_001354615.2:c.-584G>A
NM_001354616.2:c.-584G>A
NM_001354617.2:c.-676G>A
NM_001354618.2:c.-908G>A
NM_001354619.2:c.-1032G>A
NM_001354620.2:c.-242G>A
NM_001354621.2:c.-1001G>A
NM_001354622.2:c.-1114G>A
NM_001354623.2:c.-1023G>A
NM_001354624.2:c.-784G>A
NM_001354625.2:c.-682G>A
NM_001354626.2:c.-779G>A
NM_001354627.2:c.-1011G>A
NM_001354628.2:c.43G>A
NM_001354629.2:c.43G>A
NM_001354630.2:c.43G>A
NP_000240.1:p.Val15Met
NP_000240.1:p.Val15Met
NP_001245200.1:p.Val15Met
NP_001341557.1:p.Val15Met
NP_001341558.1:p.Val15Met
NP_001341559.1:p.Val15Met
LRG_216t1:c.43G>A
LRG_216:g.5241G>A
LRG_216p1:p.Val15Met
NC_000003.11:g.37035081G>A
NM_000249.3:c.43G>A

Protein change:

V15M

Links:

dbSNP: rs876660301

NCBI 1000 Genomes Browser:

rs876660301

Molecular consequence:

NM_001167617.3:c.-474G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-903G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-816G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-590G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-1053G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-584G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-584G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-676G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-908G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-1032G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-242G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-1001G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-1114G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-1023G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-784G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-682G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-779G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-1011G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.43G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001258271.2:c.43G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354628.2:c.43G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354629.2:c.43G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354630.2:c.43G>A - missense variant - [Sequence Ontology: SO:0001583]

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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PREDICTED: receptor-like serine/threonine-protein kinase At3g01300 [Ziziphus juj...
PREDICTED: receptor-like serine/threonine-protein kinase At3g01300 [Ziziphus jujuba]
gi|1009110187|ref|XP_015894187.1|

Protein
probable serine/threonine-protein kinase PIX7 [Prunus persica]
probable serine/threonine-protein kinase PIX7 [Prunus persica]
gi|595804260|ref|XP_007202128.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000277616	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely benign (Dec 16, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000277616

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely benign
(Dec 16, 2020)

germline

clinical testing

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

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

Citations

PubMed

Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome.

Wu H, Zeng H, Lam R, Tempel W, Kerr ID, Min J.

Acta Crystallogr F Struct Biol Commun. 2015 Aug;71(Pt 8):981-5. doi: 10.1107/S2053230X15010183. Epub 2015 Jul 28.

PubMed [citation]

PMID:: 26249686
PMCID:: PMC4528928

Details of each submission

From Ambry Genetics, SCV000277616.7

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

Description

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

#	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: Sep 29, 2024

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