Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000249.4(MLH1):c.1558+1G>A

CA348840

220185 (ClinVar)

Gene: MLH1
Condition: Lynch syndrome 1
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 6c10a047-21f7-4882-b455-c59254001508
Approved on: 2024-09-19
Published on: 2024-10-11

HGVS expressions

NM_000249.4:c.1558+1G>A
NM_000249.4(MLH1):c.1558+1G>A
NC_000003.12:g.37028933G>A
CM000665.2:g.37028933G>A
NC_000003.11:g.37070424G>A
CM000665.1:g.37070424G>A
NC_000003.10:g.37045428G>A
NG_007109.2:g.40584G>A
ENST00000413740.2:c.1558+1G>A
ENST00000429117.6:c.1264+1G>A
ENST00000450420.6:c.1558+1G>A
ENST00000456676.7:c.1558+1G>A
ENST00000492474.6:c.835+1G>A
ENST00000616768.6:c.1558+1G>A
ENST00000673673.2:c.1558+1G>A
ENST00000231790.8:c.1558+1G>A
ENST00000413212.2:c.*476+1G>A
ENST00000432299.6:c.*1390+1G>A
ENST00000441265.6:c.835+1G>A
ENST00000447829.6:c.*669+1G>A
ENST00000539477.6:c.835+1G>A
ENST00000616768.5:c.595+1G>A
ENST00000673673.1:c.1511+1G>A
ENST00000673715.1:c.1558+1G>A
ENST00000673889.1:n.940+1G>A
ENST00000673897.1:c.*1350+1G>A
ENST00000673899.1:c.826+1G>A
ENST00000673947.1:c.*1698+1G>A
ENST00000673972.1:c.*1436+1G>A
ENST00000673990.1:n.1449+1G>A
ENST00000674019.1:c.835+1G>A
ENST00000674107.1:n.1407G>A
ENST00000674111.1:c.1558+1G>A
ENST00000674125.1:n.269+1G>A
ENST00000231790.6:c.1558+1G>A
ENST00000413212.1:c.633+1G>A
ENST00000413740.1:c.181+1G>A
ENST00000435176.5:c.1264+1G>A
ENST00000450420.5:c.181+1G>A
ENST00000455445.6:c.835+1G>A
ENST00000456676.6:c.1533+1G>A
ENST00000458205.6:c.835+1G>A
ENST00000536378.5:c.835+1G>A
ENST00000539477.5:c.835+1G>A
ENST00000616768.4:c.326+1G>A
NM_000249.3:c.1558+1G>A
NM_001167617.1:c.1264+1G>A
NM_001167618.1:c.835+1G>A
NM_001167619.1:c.835+1G>A
NM_001258271.1:c.1558+1G>A
NM_001258273.1:c.835+1G>A
NM_001258274.1:c.835+1G>A
NM_001167617.2:c.1264+1G>A
NM_001167618.2:c.835+1G>A
NM_001167619.2:c.835+1G>A
NM_001258274.2:c.835+1G>A
NM_001354615.1:c.835+1G>A
NM_001354616.1:c.835+1G>A
NM_001354617.1:c.835+1G>A
NM_001354618.1:c.835+1G>A
NM_001354619.1:c.835+1G>A
NM_001354620.1:c.1264+1G>A
NM_001354621.1:c.535+1G>A
NM_001354622.1:c.535+1G>A
NM_001354623.1:c.535+1G>A
NM_001354624.1:c.484+1G>A
NM_001354625.1:c.484+1G>A
NM_001354626.1:c.484+1G>A
NM_001354627.1:c.484+1G>A
NM_001354628.1:c.1558+1G>A
NM_001354629.1:c.1459+1G>A
NM_001354630.1:c.1558+1G>A
NM_001167617.3:c.1264+1G>A
NM_001167618.3:c.835+1G>A
NM_001167619.3:c.835+1G>A
NM_001258271.2:c.1558+1G>A
NM_001258273.2:c.835+1G>A
NM_001258274.3:c.835+1G>A
NM_001354615.2:c.835+1G>A
NM_001354616.2:c.835+1G>A
NM_001354617.2:c.835+1G>A
NM_001354618.2:c.835+1G>A
NM_001354619.2:c.835+1G>A
NM_001354620.2:c.1264+1G>A
NM_001354621.2:c.535+1G>A
NM_001354622.2:c.535+1G>A
NM_001354623.2:c.535+1G>A
NM_001354624.2:c.484+1G>A
NM_001354625.2:c.484+1G>A
NM_001354626.2:c.484+1G>A
NM_001354627.2:c.484+1G>A
NM_001354628.2:c.1558+1G>A
NM_001354629.2:c.1459+1G>A
NM_001354630.2:c.1558+1G>A
More

Likely Pathogenic

Met criteria codes 2
PVS1 PM2_Supporting

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MLH1 Version 1.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP
The NM_000249.4(MLH1):c.1558+1G>A variant in APC affects a donor splice site in intron 13 of the MLH1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product and loss-of-function variants in MLH1 are known to be pathogenic (PVS1 met). The variant is reported once in gnomAD v4.1 (PM2_supporting met). In summary, this variant meets the criteria to be classified as likely pathogenic for autosomal-dominant inherited Lynch-syndrome based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis: criteria PVS1 and PM2_supporting applied. (VCEP specifications version 1)
Met criteria codes
PVS1
The variant in NM_000249.4(MLH1):c.1558+1G>A affects a donor splice site in intron 13 of the MLH1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product and loss-of-function variants in MLH1 are known to be pathogenic (PVS1).
PM2_Supporting
This variant is absent from gnomAD v2.1.1 and observed once in gnomAD v4.1 (PM2_Supporting).
Curation History
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