NM_000179.3(MSH6):c.3350G>T (p.Cys1117Phe) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Apr 28, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000487138.2

Allele description [Variation Report for NM_000179.3(MSH6):c.3350G>T (p.Cys1117Phe)]

NM_000179.3(MSH6):c.3350G>T (p.Cys1117Phe)

Gene:

MSH6:mutS homolog 6 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p16.3

Genomic location:

Preferred name:

NM_000179.3(MSH6):c.3350G>T (p.Cys1117Phe)

HGVS:

NC_000002.12:g.47803597G>T
NG_007111.1:g.25451G>T
NM_000179.3:c.3350G>TMANE SELECT
NM_001281492.2:c.2960G>T
NM_001281493.2:c.2444G>T
NM_001281494.2:c.2444G>T
NP_000170.1:p.Cys1117Phe
NP_000170.1:p.Cys1117Phe
NP_001268421.1:p.Cys987Phe
NP_001268422.1:p.Cys815Phe
NP_001268423.1:p.Cys815Phe
LRG_219t1:c.3350G>T
LRG_219:g.25451G>T
LRG_219p1:p.Cys1117Phe
NC_000002.11:g.48030736G>T
NM_000179.2:c.3350G>T

Protein change:

C1117F

Links:

dbSNP: rs773245315

NCBI 1000 Genomes Browser:

rs773245315

Molecular consequence:

NM_000179.3:c.3350G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281492.2:c.2960G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281493.2:c.2444G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001281494.2:c.2444G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000568034	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Sep 21, 2015)	germline	clinical testing	Citation Link,
SCV002774649	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Apr 28, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000568034

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Sep 21, 2015)

germline

clinical testing

Citation Link,

SCV002774649

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Apr 28, 2022)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From GeneDx, SCV000568034.4

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

Description

This variant is denoted MSH6 c.3350G>T at the cDNA level, p.Cys1117Phe (C1117F) at the protein level, and results in the change of a Cysteine to a Phenylalanine (TGT>TTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. MSH6 Cys1117Phe was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Cysteine and Phenylalanine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. MSH6 Cys1117Phe occurs at a position that is conserved in mammals and is not located in a known functional domain (Kariola 2002, Terui 2013). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether MSH6 Cys1117Phe is pathogenic or benign. We consider it to be a variant of uncertain significance.

#	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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV002774649.1

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

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

Last Updated: Sep 29, 2024

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