NM_000249.4(MLH1):c.925C>T (p.Pro309Ser) AND Hereditary cancer-predisposing syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Apr 2, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000574268.5

Allele description [Variation Report for NM_000249.4(MLH1):c.925C>T (p.Pro309Ser)]

NM_000249.4(MLH1):c.925C>T (p.Pro309Ser)

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.925C>T (p.Pro309Ser)
HGVS:
  • NC_000003.12:g.37020350C>T
  • NG_007109.2:g.32001C>T
  • NM_000249.3:c.925C>T
  • NM_000249.4:c.925C>TMANE SELECT
  • NM_001167617.3:c.631C>T
  • NM_001167618.3:c.202C>T
  • NM_001167619.3:c.202C>T
  • NM_001258271.2:c.925C>T
  • NM_001258273.2:c.202C>T
  • NM_001258274.3:c.202C>T
  • NM_001354615.2:c.202C>T
  • NM_001354616.2:c.202C>T
  • NM_001354617.2:c.202C>T
  • NM_001354618.2:c.202C>T
  • NM_001354619.2:c.202C>T
  • NM_001354620.2:c.631C>T
  • NM_001354621.2:c.-99C>T
  • NM_001354622.2:c.-99C>T
  • NM_001354623.2:c.-99C>T
  • NM_001354624.2:c.-36-5287C>T
  • NM_001354625.2:c.-36-5287C>T
  • NM_001354626.2:c.-36-5287C>T
  • NM_001354627.2:c.-36-5287C>T
  • NM_001354628.2:c.925C>T
  • NM_001354629.2:c.826C>T
  • NM_001354630.2:c.925C>T
  • NP_000240.1:p.Pro309Ser
  • NP_000240.1:p.Pro309Ser
  • NP_001161089.1:p.Pro211Ser
  • NP_001161090.1:p.Pro68Ser
  • NP_001161091.1:p.Pro68Ser
  • NP_001245200.1:p.Pro309Ser
  • NP_001245202.1:p.Pro68Ser
  • NP_001245203.1:p.Pro68Ser
  • NP_001341544.1:p.Pro68Ser
  • NP_001341545.1:p.Pro68Ser
  • NP_001341546.1:p.Pro68Ser
  • NP_001341547.1:p.Pro68Ser
  • NP_001341548.1:p.Pro68Ser
  • NP_001341549.1:p.Pro211Ser
  • NP_001341557.1:p.Pro309Ser
  • NP_001341558.1:p.Pro276Ser
  • NP_001341559.1:p.Pro309Ser
  • LRG_216t1:c.925C>T
  • LRG_216:g.32001C>T
  • LRG_216p1:p.Pro309Ser
  • NC_000003.11:g.37061841C>T
  • P40692:p.Pro309Ser
Protein change:
P211S
Links:
UniProtKB: P40692#VAR_038025; dbSNP: rs267607808
NCBI 1000 Genomes Browser:
rs267607808
Molecular consequence:
  • NM_001354621.2:c.-99C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354622.2:c.-99C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354623.2:c.-99C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001354624.2:c.-36-5287C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354625.2:c.-36-5287C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354626.2:c.-36-5287C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001354627.2:c.-36-5287C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000249.3:c.925C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000249.4:c.925C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001167617.3:c.631C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001167618.3:c.202C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001167619.3:c.202C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258271.2:c.925C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258273.2:c.202C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258274.3:c.202C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354615.2:c.202C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354616.2:c.202C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354617.2:c.202C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354618.2:c.202C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354619.2:c.202C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354620.2:c.631C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354628.2:c.925C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354629.2:c.826C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354630.2:c.925C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000662018Ambry Geneticscriteria provided, single submitter
Likely benign
(Jan 30, 2019)
germlineclinical testing

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

Citation Link,

SCV000689930Color Health, Inccriteria provided, single submitter
Uncertain significance
(Apr 2, 2019)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Classification of ambiguous mutations in DNA mismatch repair genes identified in a population-based study of colorectal cancer.

Barnetson RA, Cartwright N, van Vliet A, Haq N, Drew K, Farrington S, Williams N, Warner J, Campbell H, Porteous ME, Dunlop MG.

Hum Mutat. 2008 Mar;29(3):367-74.

PubMed [citation]
PMID:
18033691

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 Ambry Genetics, SCV000662018.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

Subpopulation frequency in support of benign classification

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

From Color Health, Inc, SCV000689930.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 30, 2021

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