NM_000249.4(MLH1):c.155_156del (p.Lys52fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 5, 2014
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:: RCV000160515.1

Allele description [Variation Report for NM_000249.4(MLH1):c.155_156del (p.Lys52fs)]

NM_000249.4(MLH1):c.155_156del (p.Lys52fs)

Gene:

MLH1:mutL homolog 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.155_156del (p.Lys52fs)

HGVS:

NC_000003.12:g.36996657_36996658del
NG_007109.2:g.8308_8309del
NG_008418.1:g.1648_1649del
NM_000249.4:c.155_156delMANE SELECT
NM_001167617.3:c.-135_-134del
NM_001167618.3:c.-569_-568del
NM_001167619.3:c.-477_-476del
NM_001258271.2:c.155_156del
NM_001258273.2:c.-517+2994_-517+2995del
NM_001258274.3:c.-714_-713del
NM_001354615.2:c.-472_-471del
NM_001354616.2:c.-477_-476del
NM_001354617.2:c.-569_-568del
NM_001354618.2:c.-569_-568del
NM_001354619.2:c.-569_-568del
NM_001354620.2:c.-135_-134del
NM_001354621.2:c.-662_-661del
NM_001354622.2:c.-775_-774del
NM_001354623.2:c.-723+2767_-723+2768del
NM_001354624.2:c.-672_-671del
NM_001354625.2:c.-575_-574del
NM_001354626.2:c.-672_-671del
NM_001354627.2:c.-672_-671del
NM_001354628.2:c.155_156del
NM_001354629.2:c.155_156del
NM_001354630.2:c.155_156del
NP_000240.1:p.Lys52fs
NP_001245200.1:p.Lys52fs
NP_001341557.1:p.Lys52fs
NP_001341558.1:p.Lys52fs
NP_001341559.1:p.Lys52fs
LRG_216:g.8308_8309del
NC_000003.11:g.37038148_37038149del
NM_000249.3:c.155_156delAA
p.K52RfsX26

Protein change:

K52fs

Links:

dbSNP: rs63750028

NCBI 1000 Genomes Browser:

rs63750028

Molecular consequence:

NM_001167617.3:c.-135_-134del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167618.3:c.-569_-568del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-477_-476del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-714_-713del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-472_-471del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-477_-476del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-569_-568del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-569_-568del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-569_-568del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354620.2:c.-135_-134del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-662_-661del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-775_-774del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-672_-671del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-575_-574del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-672_-671del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-672_-671del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.155_156del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258271.2:c.155_156del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354628.2:c.155_156del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354629.2:c.155_156del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354630.2:c.155_156del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258273.2:c.-517+2994_-517+2995del - intron variant - [Sequence Ontology: SO:0001627]
NM_001354623.2:c.-723+2767_-723+2768del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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597928[uid] (1)
Taxonomy
spectrin alpha chain, non-erythrocytic 1 isoform X2 [Mus musculus]
spectrin alpha chain, non-erythrocytic 1 isoform X2 [Mus musculus]
gi|568913204|ref|XP_006497873.1|

Protein
spectrin alpha chain, non-erythrocytic 1 isoform 5 [Mus musculus]
spectrin alpha chain, non-erythrocytic 1 isoform 5 [Mus musculus]
gi|1606838543|ref|NP_001356254.1|

Protein
LhbA (chloroplast) [Eremophila phyllopoda subsp. obliqua]
LhbA (chloroplast) [Eremophila phyllopoda subsp. obliqua]
gi|2666676830|ref|YP_011001912.1|

Protein
SRX7544417 (1)
SRA

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000211080	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Aug 5, 2014)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000211080

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Aug 5, 2014)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000211080.3

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

Description

This deletion of two nucleotides in MLH1 is denoted c.155_156delAA at the cDNA level and p.Lys52ArgfsX26 (K52RfsX26) at the protein level. The normal sequence, with the bases that are deleted in brackets, is GTTA[AA]GAGG. The deletion causes a frameshift, which changes a Lysine to an Arginine at codon 52, and creates a premature stop codon at position 26 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. we consider this variant to be pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 30, 2023

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