VCV000626220.2 - ClinVar

NM_000207.3(INS):c.26C>G (p.Pro9Arg)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(2)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Likely risk allele

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000207.3(INS):c.26C>G (p.Pro9Arg)

Variation ID: 626220 Accession: VCV000626220.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 11p15.5 11: 2160946 (GRCh38) [ NCBI UCSC ] 11: 2182176 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 28, 2019	Dec 11, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_000207.3:c.26C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000198.1:p.Pro9Arg	missense
NM_001042376.3:c.26C>G	NP_001035835.1:p.Pro9Arg	missense
NM_001185097.2:c.26C>G	NP_001172026.1:p.Pro9Arg	missense
NM_001185098.2:c.26C>G	NP_001172027.1:p.Pro9Arg	missense
NM_001291897.2:c.26C>G	NP_001278826.1:p.Pro9Arg	missense
NR_003512.4:n.85C>G		non-coding transcript variant
NC_000011.10:g.2160946G>C
NC_000011.9:g.2182176G>C
NG_007114.1:g.5249C>G
NG_050578.1:g.5264C>G

... more HGVS ... less HGVS

Protein change

P9R

Other names

Canonical SPDI

NC_000011.10:2160945:G:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

dbSNP: rs1564912403 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
INS		No evidence available	No evidence available	GRCh38 GRCh37	13	203
INS-IGF2	-	-	-	GRCh38 GRCh37	-	334

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Permanent neonatal diabetes mellitus	Likely pathogenic (1)	no assertion criteria provided	-	RCV000768377.1
Neonatal insulin-dependent diabetes mellitus	Likely risk allele (1)	criteria provided, single submitter	-	RCV002464311.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Likely risk allele (-)	criteria provided, single submitter (K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1) Method: research	Neonatal insulin-dependent diabetes mellitus Affected status: unknown Allele origin: unknown	Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic Accession: SCV002605411.1 First in ClinVar: Dec 11, 2022 Last updated: Dec 11, 2022	Publications: PubMed (4) PubMed: 11921414‚ 25542748‚ 26101329‚ 18171712 Comment: Mutations in INS gene can cause early onset diabetes mellitus which is insulin dependent. May have poor response to sulfonylureas, as this mutation can cause … (more) Mutations in INS gene can cause early onset diabetes mellitus which is insulin dependent. May have poor response to sulfonylureas, as this mutation can cause beta cell destruction. However no sufficient evidence is found to ascertain the role of this particular variant rs1564912403, yet. (less)
Likely pathogenic (-)	no assertion criteria provided Method: clinical testing	Permanent neonatal diabetes mellitus 1 Affected status: yes Allele origin: germline	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego Accession: SCV000898466.1 First in ClinVar: Apr 28, 2019 Last updated: Apr 28, 2019	Sex: female

Comment:

Mutations in INS gene can cause early onset diabetes mellitus which is insulin dependent. May have poor response to sulfonylureas, as this mutation can cause beta cell destruction. However no sufficient evidence is found to ascertain the role of this particular variant rs1564912403, yet.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Neonatal diabetes mellitus due to a novel variant in the INS gene.	Laurenzano SE	Cold Spring Harbor molecular case studies	2019	PMID: 31196892
Continued lessons from the INS gene: an intronic mutation causing diabetes through a novel mechanism.	Carmody D	Journal of medical genetics	2015	PMID: 26101329
INS-gene mutations: from genetics and beta cell biology to clinical disease.	Liu M	Molecular aspects of medicine	2015	PMID: 25542748
Heterozygous missense mutations in the insulin gene are linked to permanent diabetes appearing in the neonatal period or in early infancy: a report from the French ND (Neonatal Diabetes) Study Group.	Polak M	Diabetes	2008	PMID: 18171712
The insulin gene in diabetes.	Pugliese A	Diabetes/metabolism research and reviews	2002	PMID: 11921414

Text-mined citations for rs1564912403 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Sep 01, 2024

ClinVar Genomic variation as it relates to human health

NM_000207.3(INS):c.26C>G (p.Pro9Arg)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1564912403 ...