NM_153676.4(USH1C):c.2246T>C (p.Met749Thr) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 29, 2022
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:: RCV003077914.2

Allele description [Variation Report for NM_153676.4(USH1C):c.2246T>C (p.Met749Thr)]

NM_153676.4(USH1C):c.2246T>C (p.Met749Thr)

Gene:

USH1C:USH1 protein network component harmonin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.1

Genomic location:

Preferred name:

NM_153676.4(USH1C):c.2246T>C (p.Met749Thr)

HGVS:

NC_000011.10:g.17501516A>G
NG_011883.2:g.47901T>C
NM_001297764.2:c.1289T>C
NM_005709.3:c.1346T>C
NM_005709.4:c.1346T>C
NM_153676.4:c.2246T>CMANE SELECT
NP_001284693.1:p.Met430Thr
NP_005700.2:p.Met449Thr
NP_710142.1:p.Met749Thr
NC_000011.9:g.17523063A>G
NR_123738.2:n.1381T>C

Protein change:

M430T

Molecular consequence:

NM_001297764.2:c.1289T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005709.4:c.1346T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_153676.4:c.2246T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_123738.2:n.1381T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

PREDICTED: Homo sapiens caspase 8 associated protein 2 (CASP8AP2), transcript va...
PREDICTED: Homo sapiens caspase 8 associated protein 2 (CASP8AP2), transcript variant X16, mRNA
gi|2462496953|ref|XM_054332076.1|

Nucleotide
CASP8-associated protein 2 isoform X3 [Homo sapiens]
CASP8-associated protein 2 isoform X3 [Homo sapiens]
gi|2462496942|ref|XP_054188045.1|

Protein
Homo sapiens connexin 62 mRNA, complete cds
Homo sapiens connexin 62 mRNA, complete cds
gi|14009610|gb|AF296766.1|

Nucleotide
CASP8-associated protein 2 isoform X2 [Homo sapiens]
CASP8-associated protein 2 isoform X2 [Homo sapiens]
gi|2462496924|ref|XP_054188036.1|

Protein
Homo sapiens CGI-76 protein mRNA, complete cds
Homo sapiens CGI-76 protein mRNA, complete cds
gi|4929620|gb|AF151834.1|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003469067	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 29, 2022)	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

SCV003469067

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 29, 2022)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003469067.1

#	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 methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 449 of the USH1C protein (p.Met449Thr). This variant is present in population databases (rs370437884, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with USH1C-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine