VCV000464491.36 - ClinVar

NM_015335.5(MED13L):c.3866C>T (p.Pro1289Leu)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance(2); Likely benign(4)

6 out of 7 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_015335.5(MED13L):c.3866C>T (p.Pro1289Leu)

Variation ID: 464491 Accession: VCV000464491.36

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 12q24.21 12: 115991088 (GRCh38) [ NCBI UCSC ] 12: 116428893 (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	Dec 26, 2017	Jan 11, 2026	Oct 1, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_015335.5:c.3866C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_056150.1:p.Pro1289Leu	missense
NC_000012.12:g.115991088G>A
NC_000012.11:g.116428893G>A
NG_023366.1:g.291099C>T

Protein change

P1289L

Other names

Canonical SPDI

NC_000012.12:115991087: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.

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

Exome Aggregation Consortium (ExAC) 0.00018

The Genome Aggregation Database (gnomAD), exomes 0.00021

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015

The Genome Aggregation Database (gnomAD) 0.00020

The Genome Aggregation Database (gnomAD), exomes 0.00020

The Genome Aggregation Database (gnomAD) 0.00023

Trans-Omics for Precision Medicine (TOPMed) 0.00033

Links

ClinGen: CA6810925 dbSNP: rs200187663 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.
MED13L		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1671	1692

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.
Dextro-looped transposition of the great arteries	Likely benign (1)	criteria provided, single submitter	Oct 21, 2024	RCV000556168.5
not provided	Conflicting classifications of pathogenicity (3)	criteria provided, conflicting classifications	Oct 1, 2025	RCV000598209.30
See cases	Uncertain significance (1)	criteria provided, single submitter	Feb 1, 2021	RCV002252159.2
Inborn genetic diseases	Likely benign (1)	criteria provided, single submitter	Jul 31, 2022	RCV002526115.2
MED13L-related disorder	Likely benign (1)	no assertion criteria provided	Sep 7, 2022	RCV004541688.2

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.
Likely benign (Oct 21, 2024) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Dextro-looped transposition of the great arteries	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000639019.4 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

Uncertain significance (Feb 21, 2017) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015)	not provided	Eurofins Ntd Llc (ga) Accession: SCV000706445.3 First in ClinVar: Apr 02, 2018 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MED13L 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: 2 Zygosity: Single Heterozygote Sex: mixed

Likely benign (Sep 02, 2020) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Not Provided	GeneDx Accession: SCV001873770.1 First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Uncertain significance (Feb 01, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	See cases	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein Accession: SCV002522828.1 First in ClinVar: Jun 09, 2022 Last updated: Jun 09, 2022	Comment: show ACMG classification criteria: BP4 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Clinical Features: Autistic behavior (present) , Autistic behavior (present)

Likely benign (Jul 31, 2022) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Inborn genetic diseases	Ambry Genetics Accession: SCV003723712.2 First in ClinVar: Feb 07, 2023 Last updated: May 01, 2024	Comment: show This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (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 (Oct 01, 2025) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV004132029.20 First in ClinVar: Nov 20, 2023 Last updated: Jan 11, 2026	Comment: show MED13L: PP2, BS2 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 3

Likely benign (Sep 07, 2022) N Not contributing to aggregate classification	no assertion criteria provided	MED13L-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004762866.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: show This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). (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 alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MED13L	-	-	-	-

Text-mined citations for rs200187663 ...

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 Jan 17, 2026

ClinVar Genomic variation as it relates to human health

NM_015335.5(MED13L):c.3866C>T (p.Pro1289Leu)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Citations for germline classification of this variant

Text-mined citations for rs200187663 ...