ClinVar Genomic variation as it relates to human health
NM_002185.5(IL7R):c.197T>C (p.Ile66Thr)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_002185.5(IL7R):c.197T>C (p.Ile66Thr)
Variation ID: 14839 Accession: VCV000014839.30
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5p13.2 5: 35860966 (GRCh38) [ NCBI UCSC ] 5: 35861068 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Jun 9, 2014 Sep 29, 2024 Jan 23, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_002185.5:c.197T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_002176.2:p.Ile66Thr missense NR_120485.3:n.284T>C non-coding transcript variant NC_000005.10:g.35860966T>C NC_000005.9:g.35861068T>C NG_009567.1:g.9078T>C LRG_74:g.9078T>C LRG_74t1:c.197T>C - Protein change
- I66T
- Other names
- T66I
- NM_002185.5(IL7R):c.197T>C
- Canonical SPDI
- NC_000005.10:35860965:T:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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0.40016 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 0.59984
1000 Genomes Project 30x 0.60572
The Genome Aggregation Database (gnomAD), exomes 0.61832
Exome Aggregation Consortium (ExAC) 0.62787
Trans-Omics for Precision Medicine (TOPMed) 0.66604
The Genome Aggregation Database (gnomAD) 0.68368
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 | ||
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HI score
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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. |
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IL7R | - | - |
GRCh38 GRCh37 |
550 | 575 |
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. |
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Benign (6) |
reviewed by expert panel
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Jan 23, 2024 | RCV000015964.44 | |
Benign (6) |
criteria provided, multiple submitters, no conflicts
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Jan 24, 2024 | RCV000121212.15 | |
Benign (4) |
criteria provided, multiple submitters, no conflicts
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Mar 3, 2015 | RCV001701567.5 |
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. |
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Benign
(Jan 23, 2024)
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reviewed by expert panel
Method: curation
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Immunodeficiency 104
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen
FDA Recognized Database
Accession: SCV004242291.1 First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
Comment:
NM_002185.5(IL7R):c.197T>C is a missense variant predicted to cause substitution of Isoleucine by Threonine at amino acid 66 (p.Ile66Thr). The filtering allele frequency (the lower threshold … (more)
NM_002185.5(IL7R):c.197T>C is a missense variant predicted to cause substitution of Isoleucine by Threonine at amino acid 66 (p.Ile66Thr). The filtering allele frequency (the lower threshold of the 95% CI of 56371/74906 alleles) of the c.197T>C variant in IL7R is 0.7458 for African/African American chromosomes by gnomAD v.4, which is higher than the ClinGen SCID VCEP threshold (>0.00566) for BA1, and therefore meets this criterion (BA1). Additionally, 353136 homozygotes have been described. In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID, based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP. Criteria applied: BA1 (VCEP specifications version 1). (less)
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Benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Immunodeficiency 104
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001136818.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
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Benign
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Immunodeficiency 104
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000457139.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Benign
(Mar 03, 2015)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001943005.2
First in ClinVar: Sep 29, 2021 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 21326139, 30377306)
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Benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000308736.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Mar 28, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000539380.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 1 paper published in 1998 claimed variant was pathogenic for SCID based on identification in 1 proband. (less)
Method: Genome/Exome Filtration
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Benign
(-)
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criteria provided, single submitter
Method: clinical testing
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Not specified
Affected status: no
Allele origin:
germline
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Pathology and Clinical Laboratory Medicine, King Fahad Medical City
Accession: SCV001438931.1
First in ClinVar: Oct 25, 2020 Last updated: Oct 25, 2020 |
Number of individuals with the variant: 455
Ethnicity/Population group: Arab
Geographic origin: Middle East
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Benign
(Aug 19, 2021)
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criteria provided, single submitter
Method: clinical testing
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Immunodeficiency 104
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV001980923.1
First in ClinVar: Oct 21, 2021 Last updated: Oct 21, 2021 |
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Benign
(Jan 24, 2024)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan
Accession: SCV004233014.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
Comment:
This variant is classified as Benign based on local population frequency. This variant was detected in 83% of patients studied by a panel of primary … (more)
This variant is classified as Benign based on local population frequency. This variant was detected in 83% of patients studied by a panel of primary immunodeficiencies. Number of patients: 79. Only high quality variants are reported. (less)
Number of individuals with the variant: 79
Age: <18 years
Sex: mixed
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Immunodeficiency 104
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001720362.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024 |
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Benign
(-)
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criteria provided, single submitter
Method: not provided
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not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005299853.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001741359.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Uncertain significance
(Dec 01, 1998)
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no assertion criteria provided
Method: literature only
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RECLASSIFIED - VARIANT OF UNKNOWN SIGNIFICANCE
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000036231.5
First in ClinVar: Apr 04, 2013 Last updated: Sep 08, 2024 |
Comment on evidence:
This variant, formerly titled SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-POSITIVE, NK CELL-POSITIVE, has been reclassified as a variant of unknown significance based … (more)
This variant, formerly titled SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-POSITIVE, NK CELL-POSITIVE, has been reclassified as a variant of unknown significance based on a review of the ExAC database by Hamosh (2018). In a male infant (patient 1) with a primary immunodeficiency presenting as T-, B+, NK+ SCID, Puel et al. (1998) identified 2 homozygous variants in the IL7R gene: a C-to-T transition in exon 2, resulting in a thr66-to-ile (T66I) substitution, and an A-to-G transition in exon 4, resulting in an ile138-to-val (I138V; 146661.0002) substitution. The patient was homozygous and both parents were heterozygous for both variants. Each parent expressed mRNA only from the wildtype allele, and IL7R mRNA was undetectable in patient cells. However, functional studies of these variants did not reveal significant defects and the variants were present in healthy controls, indicating that T66I and I138V represent polymorphisms and were not responsible for the disease. Hamosh (2018) found that the T (minor) allele of this variant was present in 76,179 of 121,330 alleles in the ExAC database, for an allele frequency of 0.6279 (April 20, 2018), suggesting that the variant is not pathogenic. In the patient (patient 1) with a primary immunodeficiency manifest as T-, B+, NK+ SCID (IMD104; 608971) reported by Puel et al. (1998), Puel and Leonard (2000) identified a homozygous splice site mutation (146661.0007) in the IL7R gene that was responsible for the disorder. Each unaffected parent was heterozygous for the splice site mutation. Patient cells showed no detectable IL7R mRNA, consistent with complete IL7R deficiency. (less)
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001927865.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000085383.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
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Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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not provided
(-)
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no classification provided
Method: phenotyping only
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Not Provided
Affected status: unknown
Allele origin:
unknown
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GenomeConnect, ClinGen
Accession: SCV002074670.1
First in ClinVar: Feb 11, 2022 Last updated: Feb 11, 2022 |
Comment:
Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided … (more)
Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. (less)
Clinical Features:
Phenotypic abnormality (present)
Indication for testing: Diagnostic
Age: 40-49 years
Sex: female
Testing laboratory: Invitae
Date variant was reported to submitter: 2020-04-27
Testing laboratory interpretation: Benign
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Mutations in the gene for the IL-7 receptor result in T(-)B(+)NK(+) severe combined immunodeficiency disease. | Puel A | Current opinion in immunology | 2000 | PMID: 10899029 |
Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency. | Puel A | Nature genetics | 1998 | PMID: 9843216 |
Hamosh, A. Personal Communication. 2018. Baltimore, Md. | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/c8cc977c-3f8e-47b1-91a6-280d5a93d09b | - | - | - | - |
Text-mined citations for rs1494558 ...
HelpRecord last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.