VCV000044066.24 - ClinVar

NM_001145809.2(MYH14):c.3468-3C>T

Germline

Classification

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

Benign

8 out of 9 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_001145809.2(MYH14):c.3468-3C>T

Variation ID: 44066 Accession: VCV000044066.24

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19q13.33 19: 50275988 (GRCh38) [ NCBI UCSC ] 19: 50779245 (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	Sep 22, 2014	Jun 8, 2025	Feb 3, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001145809.2:c.3468-3C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_001077186.2:c.3369-3C>T		intron variant
NM_024729.4:c.3345-3C>T		intron variant
NC_000019.10:g.50275988C>T
NC_000019.9:g.50779245C>T
NG_011645.1:g.77361C>T

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000019.10:50275987:C:T

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.

0.00859 (T)

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

The Genome Aggregation Database (gnomAD) 0.01689

1000 Genomes Project 30x 0.00874

Trans-Omics for Precision Medicine (TOPMed) 0.01787

The Genome Aggregation Database (gnomAD) 0.01724

The Genome Aggregation Database (gnomAD), exomes 0.01767

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01934

Exome Aggregation Consortium (ExAC) 0.02043

The Genome Aggregation Database (gnomAD), exomes 0.02312

1000 Genomes Project 0.00859

Links

ClinGen: CA210875 dbSNP: rs78192108 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.
MYH14		-	-	GRCh38 GRCh37	1367	1406

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.
Autosomal dominant nonsyndromic hearing loss 4A	Benign (2)	criteria provided, single submitter	Jan 13, 2018	RCV000144089.9
not specified	Benign (4)	criteria provided, multiple submitters, no conflicts	Nov 21, 2017	RCV000037042.16
not provided	Benign (3)	criteria provided, multiple submitters, no conflicts	Feb 3, 2025	RCV000992390.9

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 (Apr 30, 2012) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000060698.5 First in ClinVar: May 03, 2013 Last updated: Apr 09, 2018	Comment: 3468-3C>T in Intron 27 of MYH14: This variant is not expected to have clinical s ignificance because it has been identified in 2.5% (165/6628) of … (more) 3468-3C>T in Intron 27 of MYH14: This variant is not expected to have clinical s ignificance because it has been identified in 2.5% (165/6628) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs78192108). (less) Number of individuals with the variant: 59

Benign (Mar 13, 2019) C Contributing to aggregate classification	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV001144627.1 First in ClinVar: Jan 19, 2020 Last updated: Jan 19, 2020

Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005309777.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024

Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000306864.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016

Benign (Nov 21, 2017) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000730005.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	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 (Feb 03, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002407677.4 First in ClinVar: Apr 08, 2022 Last updated: Feb 25, 2025

Benign (Jan 13, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Autosomal dominant nonsyndromic hearing loss 4A Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000414421.3 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)

Benign (Feb 09, 2015) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000228386.6 First in ClinVar: Jun 28, 2015 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MYH14 Number of individuals with the variant: 6 Zygosity: Single Heterozygote Sex: mixed

not provided (-) N Not contributing to aggregate classification	no classification provided Method: not provided	Deafness, autosomal dominant 4 Affected status: not provided Allele origin: somatic	Genomic Research Center, Shahid Beheshti University of Medical Sciences Accession: SCV000189163.2 First in ClinVar: Sep 22, 2014 Last updated: Jun 08, 2025 Comment: rs78192108	Comment: Converted during submission from untested to not provided.

Comment:

3468-3C>T in Intron 27 of MYH14: This variant is not expected to have clinical s ignificance because it has been identified in 2.5% (165/6628) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs78192108).

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 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.

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
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MYH14	-	-	-	-

Text-mined citations for rs78192108 ...

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 Jun 08, 2025

ClinVar Genomic variation as it relates to human health

NM_001145809.2(MYH14):c.3468-3C>T

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs78192108 ...