NM_000249.4(MLH1):c.640del (p.Asp214fs) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 23, 2017
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:: RCV000657346.1

Allele description [Variation Report for NM_000249.4(MLH1):c.640del (p.Asp214fs)]

NM_000249.4(MLH1):c.640del (p.Asp214fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

3p22.2

Genomic location:

Preferred name:

NM_000249.4(MLH1):c.640del (p.Asp214fs)

HGVS:

NC_000003.12:g.37012062del
NG_007109.2:g.23713del
NM_000249.4:c.640delMANE SELECT
NM_001167617.3:c.346del
NM_001167618.3:c.-84del
NM_001167619.3:c.-84del
NM_001258271.2:c.640del
NM_001258273.2:c.-84del
NM_001258274.3:c.-84del
NM_001354615.2:c.-84del
NM_001354616.2:c.-84del
NM_001354617.2:c.-84del
NM_001354618.2:c.-84del
NM_001354619.2:c.-84del
NM_001354620.2:c.346del
NM_001354621.2:c.-177del
NM_001354622.2:c.-290del
NM_001354623.2:c.-290del
NM_001354624.2:c.-187del
NM_001354625.2:c.-187del
NM_001354626.2:c.-187del
NM_001354627.2:c.-187del
NM_001354628.2:c.640del
NM_001354629.2:c.541del
NM_001354630.2:c.640del
NP_000240.1:p.Asp214fs
NP_001161089.1:p.Asp116fs
NP_001245200.1:p.Asp214fs
NP_001341549.1:p.Asp116fs
NP_001341557.1:p.Asp214fs
NP_001341558.1:p.Asp181fs
NP_001341559.1:p.Asp214fs
LRG_216:g.23713del
NC_000003.11:g.37053553del
NM_000249.3:c.640delG

Protein change:

D116fs

Links:

dbSNP: rs1553644194

NCBI 1000 Genomes Browser:

rs1553644194

Molecular consequence:

NM_001167618.3:c.-84del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001167619.3:c.-84del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258273.2:c.-84del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001258274.3:c.-84del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354615.2:c.-84del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354616.2:c.-84del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354617.2:c.-84del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354618.2:c.-84del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354619.2:c.-84del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354621.2:c.-177del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354622.2:c.-290del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354623.2:c.-290del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354624.2:c.-187del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354625.2:c.-187del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354626.2:c.-187del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001354627.2:c.-187del - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000249.4:c.640del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001167617.3:c.346del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001258271.2:c.640del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354620.2:c.346del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354628.2:c.640del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354629.2:c.541del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001354630.2:c.640del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

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LPA lipoprotein(a) [Homo sapiens]
LPA lipoprotein(a) [Homo sapiens]
Gene ID:4018

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000779078	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jun 23, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000779078

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jun 23, 2017)

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, SCV000779078.2

#	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 one nucleotide in MLH1 is denoted c.640delG at the cDNA level and p.Asp214ThrfsX15 (D214TfsX15) at the protein level. The normal sequence, with the base that is deleted in brackets, is CGTG[delG]ACAA. The deletion causes a frameshift, which changes an Aspartic Acid to a Threonine at codon 214 and creates a premature stop codon at position 15 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: Nov 5, 2022

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