ClinVar Genomic variation as it relates to human health
NM_001384474.1(LOXHD1):c.4217C>T (p.Ala1406Val)
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.
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.
Uncertain significance(1); Benign(6); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001384474.1(LOXHD1):c.4217C>T (p.Ala1406Val)
Variation ID: 178397 Accession: VCV000178397.32
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 18q21.1 18: 46533320 (GRCh38) [ NCBI UCSC ] 18: 44113283 (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 Oct 2, 2016 Mar 10, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001384474.1:c.4217C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001371403.1:p.Ala1406Val missense NM_001145472.3:c.884C>T NP_001138944.1:p.Ala295Val missense NM_001308013.2:c.596C>T NP_001294942.1:p.Ala199Val missense NM_144612.7:c.4217C>T NP_653213.6:p.Ala1406Val missense NC_000018.10:g.46533320G>A NC_000018.9:g.44113283G>A NG_016646.2:g.128714C>T - Protein change
- A1406V, A199V, A295V
- Other names
- -
- Canonical SPDI
- NC_000018.10:46533319:G:A
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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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0.00639 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00111
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00153
Trans-Omics for Precision Medicine (TOPMed) 0.00215
The Genome Aggregation Database (gnomAD), exomes 0.00399
1000 Genomes Project 30x 0.00547
1000 Genomes Project 0.00639
Exome Aggregation Consortium (ExAC) 0.00792
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
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. |
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LOXHD1 | - | - |
GRCh38 GRCh37 |
2462 | 2509 |
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/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Jan 26, 2018 | RCV000155145.14 | |
Conflicting interpretations of pathogenicity (5) |
criteria provided, conflicting classifications
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May 18, 2021 | RCV000415314.11 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Feb 1, 2024 | RCV000839248.14 |
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
(-)
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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: SCV000316010.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Likely benign
(Mar 06, 2017)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 77
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000790111.1
First in ClinVar: Jan 13, 2017 Last updated: Jan 13, 2017 |
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Benign
(May 04, 2018)
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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: SCV000981137.1
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)
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Benign
(Jan 20, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000204831.4
First in ClinVar: Jan 31, 2015 Last updated: Oct 02, 2016 |
Comment:
p.Ala1406Val in exon 28 LOXHD1: This variant is not expected to have clinical si gnificance because it has been identified in 1.9% (148/7908) of South … (more)
p.Ala1406Val in exon 28 LOXHD1: This variant is not expected to have clinical si gnificance because it has been identified in 1.9% (148/7908) of South Asian chro mosomes with 5 homozygotes by the Exome Aggregation Consortium (ExAC, http://exa c.broadinstitute.org; dbSNP rs146739496). (less)
Number of individuals with the variant: 5
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Uncertain significance
(Jan 13, 2018)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 77
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001281844.1
First in ClinVar: May 31, 2020 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (less)
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001037675.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
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Benign
(Jul 01, 2023)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004010974.5
First in ClinVar: Jul 16, 2023 Last updated: Mar 10, 2024 |
Comment:
LOXHD1: BP4, BS1, BS2
Number of individuals with the variant: 3
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Likely benign
(Jan 26, 2018)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000859147.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
Number of individuals with the variant: 1
Sex: mixed
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Benign
(May 18, 2021)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 77
Affected status: no
Allele origin:
germline
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Pars Genome Lab
Accession: SCV001736772.1
First in ClinVar: Jun 19, 2021 Last updated: Jun 19, 2021 |
Sex: mixed
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Uncertain significance
(Jan 29, 2016)
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no assertion criteria provided
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 77
(Autosomal recessive inheritance)
Affected status: unknown, yes
Allele origin:
maternal,
germline
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Baylor Genetics
Accession: SCV000328766.1
First in ClinVar: Jan 13, 2017 Last updated: Jan 13, 2017 |
Comment:
Our laboratory reported dual molecular diagnoses in PUF60 (NM_001271099.1, c.1381-2A>G) and LOXHD1 (NM_144612.6, c.4217C>T and c.442A>T in trans) in one individual with reported features which … (more)
Our laboratory reported dual molecular diagnoses in PUF60 (NM_001271099.1, c.1381-2A>G) and LOXHD1 (NM_144612.6, c.4217C>T and c.442A>T in trans) in one individual with reported features which include delayed motor milestones, delayed speech, intellectual disability, bilateral sensorineural hearing loss, febrile seizures, dysmorphic features, short stature, failure to thrive, and abnormal visual tracking. Heterozygotes for the LOXHD1 variants would not be expected to be affected. (less)
Observation 1:
Number of individuals with the variant: 1
Age: 10-19 years
Sex: male
Observation 2:
Number of individuals with the variant: 47
Age: 0-69 years
Sex: mixed
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Benign
(Jan 09, 2020)
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no assertion criteria provided
Method: clinical testing
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Autosomal recessive deafness type 77
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001455687.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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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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Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss. | Sloan-Heggen CM | Human genetics | 2016 | PMID: 26969326 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=LOXHD1 | - | - | - | - |
Text-mined citations for rs146739496 ...
HelpRecord last updated Mar 11, 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.