VCV000095174.24 - ClinVar

NM_133642.5(LARGE1):c.309C>T (p.Ser103=)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign/Likely benign

7 out of 8 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_133642.5(LARGE1):c.309C>T (p.Ser103=)

Variation ID: 95174 Accession: VCV000095174.24

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 22q12.3 22: 33650466 (GRCh38) [ NCBI UCSC ] 22: 34046452 (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	Nov 23, 2014	Apr 13, 2025	Feb 1, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_133642.5:c.309C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_598397.1:p.Ser103=	synonymous
NM_001362949.2:c.309C>T	NP_001349878.1:p.Ser103=	synonymous
NM_001362951.2:c.309C>T	NP_001349880.1:p.Ser103=	synonymous
NM_001362953.2:c.309C>T	NP_001349882.1:p.Ser103=	synonymous
NM_001378624.1:c.309C>T	NP_001365553.1:p.Ser103=	synonymous
NM_001378625.1:c.309C>T	NP_001365554.1:p.Ser103=	synonymous
NM_001378626.1:c.309C>T	NP_001365555.1:p.Ser103=	synonymous
NM_001378627.1:c.309C>T	NP_001365556.1:p.Ser103=	synonymous
NM_001378628.1:c.309C>T	NP_001365557.1:p.Ser103=	synonymous
NM_001378629.1:c.309C>T	NP_001365558.1:p.Ser103=	synonymous
NM_004737.7:c.309C>T	NP_004728.1:p.Ser103=	synonymous
NC_000022.11:g.33650466G>A
NC_000022.10:g.34046452G>A
NG_009929.2:g.274963C>T
LRG_856:g.274963C>T
LRG_856t1:c.309C>T	LRG_856p1:p.Ser103=
LRG_856t2:c.309C>T	LRG_856p2:p.Ser103=

... more HGVS ... less HGVS

Protein change

Other names

p.S103S:TCC>TCT

Canonical SPDI

NC_000022.11:33650465:G:A

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.

0.02276 (A)

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

The Genome Aggregation Database (gnomAD), exomes 0.00173

The Genome Aggregation Database (gnomAD), exomes 0.00457

Exome Aggregation Consortium (ExAC) 0.00564

The Genome Aggregation Database (gnomAD) 0.01803

The Genome Aggregation Database (gnomAD) 0.01920

Trans-Omics for Precision Medicine (TOPMed) 0.01988

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.02014

1000 Genomes Project 0.02276

1000 Genomes Project 30x 0.02514

Links

ClinGen: CA285638 dbSNP: rs59349720 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.
LARGE1		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	1059	1093

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.
not specified	Benign (4)	criteria provided, multiple submitters, no conflicts	Jun 25, 2014	RCV000081180.22
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A6	Likely benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV000320123.6
Muscular dystrophy-dystroglycanopathy type B6	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Feb 1, 2025	RCV000544713.17
not provided	Likely benign (1)	criteria provided, single submitter	-	RCV004703226.1

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.	Expand all rows Collapse all rows 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 (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	NOT SPECIFIED	PreventionGenetics, part of Exact Sciences Accession: SCV000310642.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided (Autosomal recessive inheritance)	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005210394.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024	Observation: 1 Collection method: not provided Allele origin: germline Affected status: yes Observation 1 Collection method: not provided Allele origin: germline Affected status: yes

Benign (Feb 01, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Muscular dystrophy-dystroglycanopathy type B6	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000638998.9 First in ClinVar: Dec 26, 2017 Last updated: Feb 25, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Jun 25, 2014) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015))	not specified	GeneDx Accession: SCV000196852.9 First in ClinVar: Jan 23, 2015 Last updated: Oct 02, 2016	Comment: show 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) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A6	Illumina Laboratory Services, Illumina Accession: SCV000438175.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Muscular dystrophy-dystroglycanopathy type B6	Illumina Laboratory Services, Illumina Accession: SCV000438174.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Nov 15, 2012) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015)	not specified	Eurofins Ntd Llc (ga) Accession: SCV000113088.9 First in ClinVar: Jan 17, 2014 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=LARGE1 Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 1 Zygosity: Single Heterozygote Sex: mixed

Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not specified (Autosomal recessive inheritance)	Genetic Services Laboratory, University of Chicago Accession: SCV000193514.1 First in ClinVar: Nov 23, 2014 Last updated: Nov 23, 2014 Comment: Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated … (more) Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed (less)	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

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 was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=LARGE1	-	-	-	-

Text-mined citations for rs59349720 ...

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 May 17, 2025

ClinVar Genomic variation as it relates to human health

NM_133642.5(LARGE1):c.309C>T (p.Ser103=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Citations for germline classification of this variant

Text-mined citations for rs59349720 ...