NM_194248.3(OTOF):c.4216G>A (p.Asp1406Asn) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 15, 2024
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001852849.10

Allele description [Variation Report for NM_194248.3(OTOF):c.4216G>A (p.Asp1406Asn)]

NM_194248.3(OTOF):c.4216G>A (p.Asp1406Asn)

Gene:

OTOF:otoferlin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p23.3

Genomic location:

Preferred name:

NM_194248.3(OTOF):c.4216G>A (p.Asp1406Asn)

HGVS:

NC_000002.12:g.26467376C>T
NG_009937.1:g.96323G>A
NM_001287489.2:c.4216G>A
NM_004802.4:c.1915G>A
NM_194248.3:c.4216G>AMANE SELECT
NM_194322.3:c.2146G>A
NM_194323.3:c.1915G>A
NP_001274418.1:p.Asp1406Asn
NP_004793.2:p.Asp639Asn
NP_919224.1:p.Asp1406Asn
NP_919303.1:p.Asp716Asn
NP_919304.1:p.Asp639Asn
NC_000002.11:g.26690244C>T
NM_194248.2:c.4216G>A
c.4216G>A

Protein change:

D1406N

Links:

dbSNP: rs111033352

NCBI 1000 Genomes Browser:

rs111033352

Molecular consequence:

NM_001287489.2:c.4216G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004802.4:c.1915G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_194248.3:c.4216G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_194322.3:c.2146G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_194323.3:c.1915G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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centromere protein U [Rattus norvegicus]
centromere protein U [Rattus norvegicus]
gi|71043842|ref|NP_001020844.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002130075	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Jan 15, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002499852	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (May 3, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002130075

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Jan 15, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002499852

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(May 3, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002130075.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV002499852.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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