NM_000207.3(INS):c.308A>G (p.Tyr103Cys) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 6, 2021
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:: RCV001854250.5

Allele description [Variation Report for NM_000207.3(INS):c.308A>G (p.Tyr103Cys)]

NM_000207.3(INS):c.308A>G (p.Tyr103Cys)

Genes:

INS-IGF2:INS-IGF2 readthrough [Gene - HGNC]
INS:insulin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p15.5

Genomic location:

Preferred name:

NM_000207.3(INS):c.308A>G (p.Tyr103Cys)

HGVS:

NC_000011.10:g.2159877T>C
NG_007114.1:g.6318A>G
NG_050578.1:g.6333A>G
NM_000207.3:c.308A>GMANE SELECT
NM_001042376.3:c.187+908A>G
NM_001185097.2:c.308A>G
NM_001185098.2:c.308A>G
NM_001291897.2:c.308A>G
NP_000198.1:p.Tyr103Cys
NP_001172026.1:p.Tyr103Cys
NP_001172027.1:p.Tyr103Cys
NP_001278826.1:p.Tyr103Cys
NC_000011.9:g.2181107T>C
NM_000207.2:c.308A>G
P01308:p.Tyr103Cys

Protein change:

Y103C

Links:

UniProtKB: P01308#VAR_063740; UniProtKB/Swiss-Prot: VAR_063740; dbSNP: rs121908277

NCBI 1000 Genomes Browser:

rs121908277

Molecular consequence:

NM_001042376.3:c.187+908A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000207.3:c.308A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001185097.2:c.308A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001185098.2:c.308A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001291897.2:c.308A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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PREDICTED: Mus musculus tetraspanin 4 (Tspan4), transcript variant X3, mRNA
PREDICTED: Mus musculus tetraspanin 4 (Tspan4), transcript variant X3, mRNA
gi|1907183283|ref|XM_036153326.1|

Nucleotide
uncharacterized protein [Arabidopsis thaliana]
uncharacterized protein [Arabidopsis thaliana]
Gene ID:833814

Gene
Mitochondrial transcription termination factor family protein [Arabidopsis thal...
Mitochondrial transcription termination factor family protein [Arabidopsis thaliana]
Gene ID:827709

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002179255	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 6, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 18162506, 30191644, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002179255

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 6, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthood.

Edghill EL, Flanagan SE, Patch AM, Boustred C, Parrish A, Shields B, Shepherd MH, Hussain K, Kapoor RR, Malecki M, MacDonald MJ, Støy J, Steiner DF, Philipson LH, Bell GI; Neonatal Diabetes International Collaborative Group., Hattersley AT, Ellard S.

Diabetes. 2008 Apr;57(4):1034-42. Epub 2007 Dec 27.

PubMed [citation]

PMID:: 18162506
PMCID:: PMC7611804

Comprehensive genetic screening: The prevalence of maturity-onset diabetes of the young gene variants in a population-based childhood diabetes cohort.

Johnson SR, Ellis JJ, Leo PJ, Anderson LK, Ganti U, Harris JE, Curran JA, McInerney-Leo AM, Paramalingam N, Song X, Conwell LS, Harris M, Jones TW, Brown MA, Davis EA, Duncan EL.

Pediatr Diabetes. 2019 Feb;20(1):57-64. doi: 10.1111/pedi.12766. Epub 2018 Nov 14.

PubMed [citation]

PMID:: 30191644

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002179255.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 103 of the INS protein (p.Tyr103Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with autosomal dominant permanent neonatal diabetes mellitus and/or INS-related conditions (PMID: 18162506, 30191644). ClinVar contains an entry for this variant (Variation ID: 68732). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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

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