NM_005982.4(SIX1):c.419G>A (p.Arg140Gln) AND multiple conditions

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 14, 2023
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:: RCV002038989.3

Allele description

NM_005982.4(SIX1):c.419G>A (p.Arg140Gln)

Gene:

SIX1:SIX homeobox 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q23.1

Genomic location:

Preferred name:

NM_005982.4(SIX1):c.419G>A (p.Arg140Gln)

HGVS:

NC_000014.9:g.60648771C>T
NG_008231.1:g.5667G>A
NM_005982.4:c.419G>AMANE SELECT
NP_005973.1:p.Arg140Gln
NC_000014.8:g.61115489C>T

Protein change:

R140Q

Links:

dbSNP: rs2140241105

NCBI 1000 Genomes Browser:

rs2140241105

Molecular consequence:

NM_005982.4:c.419G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Branchiootic syndrome 3 (BOS3)
Synonyms:: BO SYNDROME 3
Identifiers:: MONDO: MONDO:0012025; MedGen: C1842124; OMIM: 608389

Name:: Autosomal dominant nonsyndromic hearing loss 23
Synonyms:: Deafness, autosomal dominant 23
Identifiers:: MONDO: MONDO:0011519; MedGen: C1854594; Orphanet: 90635; OMIM: 605192

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002313700	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 14, 2023)	germline	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

SCV002313700

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 14, 2023)

germline

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV002313700.3

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

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 140 of the SIX1 protein (p.Arg140Gln). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SIX1 protein function. ClinVar contains an entry for this variant (Variation ID: 1523586). This variant has not been reported in the literature in individuals affected with SIX1-related conditions. This variant is not present in population databases (gnomAD no frequency).

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

Last Updated: Mar 5, 2024

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Relating variation to medicine