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NM_000249.4(MLH1):c.1577A>G (p.His526Arg)

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Interpretation:
Conflicting interpretations of pathogenicity​

Likely benign(1);Uncertain significance(2)

Review status:
criteria provided, conflicting interpretations
Submissions:
3 (Most recent: Jun 11, 2021)
Last evaluated:
Oct 14, 2020
Accession:
VCV000455395.8
Variation ID:
455395
Description:
single nucleotide variant
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NM_000249.4(MLH1):c.1577A>G (p.His526Arg)

Allele ID
452477
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
3p22.2
Genomic location
3: 37040204 (GRCh38) GRCh38 UCSC
3: 37081695 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
LRG_216:g.51855A>G
LRG_216t1:c.1577A>G LRG_216p1:p.His526Arg
NC_000003.12:g.37040204A>G
... more HGVS
Protein change
H526R, H168R, H285R, H493R, H185R, H428R
Other names
-
Canonical SPDI
NC_000003.12:37040203:A:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00006
The Genome Aggregation Database (gnomAD) 0.00002
Links
ClinGen: CA352059778
dbSNP: rs1304802474
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 Oct 14, 2020 RCV000558495.4
Conflicting interpretations of pathogenicity 2 criteria provided, conflicting interpretations Sep 15, 2020 RCV000775867.3
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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
Likely benign
(Aug 31, 2019)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Ambry Genetics
Accession: SCV001172671.2
Submitted: (Nov 30, 2020)
Evidence details
Comment:
Other strong data supporting benign classification
Uncertain significance
(Oct 14, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary nonpolyposis colorectal neoplasms
Allele origin: germline
Invitae
Accession: SCV000625084.4
Submitted: (Jan 07, 2021)
Evidence details
Comment:
This sequence change replaces histidine with arginine at codon 526 of the MLH1 protein (p.His526Arg). The histidine residue is weakly conserved and there is a … (more)
Uncertain significance
(Sep 15, 2020)
criteria provided, single submitter
Method: clinical testing
Hereditary cancer-predisposing syndrome
Allele origin: germline
Color Health, Inc
Accession: SCV000910342.2
Submitted: (Jun 11, 2021)
Evidence details
Comment:
This missense variant replaces histidine with arginine at codon 526 of the MLH1 protein. Computational prediction suggests that this variant may not impact protein structure … (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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There are no citations in ClinVar for this variation. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs1304802474...

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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