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NM_000249.4(MLH1):c.1136A>C (p.Tyr379Ser)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(3)

Review status:
criteria provided, conflicting interpretations
Submissions:
4 (Most recent: Jan 7, 2021)
Last evaluated:
Oct 4, 2020
Accession:
VCV000187221.8
Variation ID:
187221
Description:
single nucleotide variant
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NM_000249.4(MLH1):c.1136A>C (p.Tyr379Ser)

Allele ID
182258
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.2
Genomic location
3: 37025734 (GRCh38) GRCh38 UCSC
3: 37067225 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_216:g.37385A>C
LRG_216t1:c.1136A>C LRG_216p1:p.Tyr379Ser
NC_000003.12:g.37025734A>C
... more HGVS
Protein change
Y379S, Y281S, Y346S, Y138S, Y21S, Y38S
Other names
-
Canonical SPDI
NC_000003.12:37025733:A:C
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00003
Links
ClinGen: CA004428
dbSNP: rs143009528
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Uncertain significance 1 criteria provided, single submitter Jan 9, 2017 RCV000481402.1
Uncertain significance 1 criteria provided, single submitter Oct 4, 2020 RCV000805743.3
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Jun 11, 2018 RCV000166929.3
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
MLH1 Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
3503 3539

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Uncertain significance
(Jun 11, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV000217748.5
Submitted: (Nov 30, 2020)
Evidence details
Publications
PubMed (1)
Comment:
<p style="text-align:justify">The p.Y379S variant (also known as c.1136A>C), located in coding exon 12 of the MLH1 gene, results from an A to C substitution at … (more)
Uncertain significance
(Jan 09, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000572658.4
Submitted: (Jan 29, 2019)
Evidence details
Comment:
This variant is denoted MLH1 c.1136A>C at the cDNA level, p.Tyr379Ser (Y379S) at the protein level, and results in the change of a Tyrosine to … (more)
Likely benign
(Jan 13, 2017)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000904057.1
Submitted: (Nov 06, 2018)
Evidence details
Uncertain significance
(Oct 04, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV000945711.3
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (1)
Comment:
This sequence change replaces tyrosine with serine at codon 379 of the MLH1 protein (p.Tyr379Ser). The tyrosine residue is highly conserved and there is a … (more)

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Identification of a mutL‑homolog 1 mutation via whole‑exome sequencing in a Chinese family with Gardner syndrome. Lv Z Molecular medicine reports 2018 PMID: 29845239

Text-mined citations for rs143009528...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Dec 04, 2021