VCV000156440.30 - ClinVar

NM_000146.4(FTL):c.163T>C (p.Leu55=)

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.

(19)

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.

Benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000146.4(FTL):c.163T>C (p.Leu55=)

Variation ID: 156440 Accession: VCV000156440.30

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19q13.33 19: 48965830 (GRCh38) [ NCBI UCSC ] 19: 49469087 (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	Oct 14, 2014	Sep 29, 2024	Jul 31, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000146.4:c.163T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000137.2:p.Leu55=	synonymous
NC_000019.10:g.48965830T>C
NC_000019.9:g.49469087T>C
NG_008152.1:g.5522T>C

Protein change

Other names

Canonical SPDI

NC_000019.10:48965829:T: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.

0.46066 (C)

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

1000 Genomes Project 0.46066

1000 Genomes Project 30x 0.46237

Exome Aggregation Consortium (ExAC) 0.49791

The Genome Aggregation Database (gnomAD), exomes 0.50097

The Genome Aggregation Database (gnomAD) 0.51379

Trans-Omics for Precision Medicine (TOPMed) 0.51710

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.51953

Links

ClinGen: CA172201 dbSNP: rs2230267 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.
FTL		No evidence available	No evidence available	GRCh38 GRCh37	170	216
GYS1		-	-	GRCh38 GRCh37	595	661

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.
sporadic abdominal aortic aneurysm	Likely pathogenic (1)	no assertion criteria provided	Sep 21, 2014	RCV000144503.4
not specified	Benign (8)	criteria provided, multiple submitters, no conflicts	Jul 31, 2024	RCV000146000.19
Hereditary hyperferritinemia with congenital cataracts	Benign (3)	criteria provided, multiple submitters, no conflicts	Aug 10, 2021	RCV000369896.9
Neuroferritinopathy	Benign (2)	criteria provided, multiple submitters, no conflicts	Aug 10, 2021	RCV000315169.8
Glycogen storage disease due to muscle and heart glycogen synthase deficiency	Benign (1)	criteria provided, single submitter	Jun 14, 2016	RCV000370536.6
not provided	Benign (2)	criteria provided, multiple submitters, no conflicts	Mar 24, 2018	RCV000839535.3
L-ferritin deficiency	Benign (1)	criteria provided, single submitter	Aug 10, 2021	RCV001701526.3
Hereditary hyperferritinemia with congenital cataracts Neuroferritinopathy	Benign (1)	criteria provided, single submitter	Jan 31, 2024	RCV001516688.8

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.
Benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Hyperferritinemia Cataract Syndrome Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000414211.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Glycogen Storage Disease Type 0, Muscle Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000483740.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Neuroferritinopathy Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000414210.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Benign (Jan 31, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Neuroferritinopathy Hereditary hyperferritinemia with congenital cataracts Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001725001.4 First in ClinVar: Jun 15, 2021 Last updated: Feb 28, 2024
Benign (Aug 15, 2013)	criteria provided, single submitter (ACMG Guidelines, 2007) Method: clinical testing	not specified (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000193149.1 First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014
Benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Hereditary hyperferritinemia with congenital cataracts Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001141117.1 First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005306859.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000302651.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Mar 24, 2018)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000981436.1 First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Benign (Aug 10, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary hyperferritinemia with congenital cataracts Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001933662.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021
Benign (Aug 10, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	L-ferritin deficiency Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001933664.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021
Benign (Aug 10, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Neuroferritinopathy Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV001933665.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021
Benign (Jul 31, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: no Allele origin: germline	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan Accession: SCV005091891.1 First in ClinVar: Aug 04, 2024 Last updated: Aug 04, 2024	Comment: This variant is classified as Benign based on local population frequency. This variant was detected in 74% of patients studied in a panel designed for … (more) This variant is classified as Benign based on local population frequency. This variant was detected in 74% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 69. Only high quality variants are reported. (less) Number of individuals with the variant: 69 Age: <18 years Sex: mixed
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001954857.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Likely pathogenic (Sep 21, 2014)	no assertion criteria provided Method: research	sporadic abdominal aortic aneurysm Affected status: yes Allele origin: unknown	TilsonLab, Columbia University Accession: SCV000189822.1 First in ClinVar: Oct 14, 2014 Last updated: Oct 14, 2014 Comment: Abdominal Aortic Aneurysm (AAA) Mutations/Polymorphisms	Publications: PubMed (1) PubMed: 17182944 Comment: Observed frequency is 15/19 = 0.789 patients with abdominal aortic aneurysm versus heterozygosity is described in "Variation Viewer" as 0.496. Number of individuals with the variant: 15
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, Amsterdam University Medical Center Study: VKGL Data-share Consensus Accession: SCV001807191.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001744626.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001975448.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV002034272.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021
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Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

This variant is classified as Benign based on local population frequency. This variant was detected in 74% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 69. Only high quality variants are reported.

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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs2230267 ...

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 29, 2024

ClinVar Genomic variation as it relates to human health

NM_000146.4(FTL):c.163T>C (p.Leu55=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs2230267 ...