NM_144672.4(OTOA):c.1249C>T (p.Leu417Phe) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Jun 13, 2022
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:: RCV001868768.16

Allele description [Variation Report for NM_144672.4(OTOA):c.1249C>T (p.Leu417Phe)]

NM_144672.4(OTOA):c.1249C>T (p.Leu417Phe)

Gene:

OTOA:otoancorin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p12.2

Genomic location:

Preferred name:

NM_144672.4(OTOA):c.1249C>T (p.Leu417Phe)

Other names:

p.Leu417Phe

HGVS:

NC_000016.10:g.21710032C>T
NG_012973.2:g.50900C>T
NM_001161683.2:c.1012C>T
NM_144672.4:c.1249C>TMANE SELECT
NM_170664.3:c.277C>T
NP_001155155.1:p.Leu338Phe
NP_653273.3:p.Leu417Phe
NP_733764.1:p.Leu93Phe
NC_000016.9:g.21721353C>T
NM_144672.3:c.1249C>T

Protein change:

L338F

Links:

dbSNP: rs764182550

NCBI 1000 Genomes Browser:

rs764182550

Molecular consequence:

NM_001161683.2:c.1012C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_144672.4:c.1249C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_170664.3:c.277C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002009998	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 3, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002222419	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23897863, 28492532
SCV004227538	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 19, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002009998

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Nov 3, 2021)

germline

clinical testing

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

SCV002222419

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 13, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV004227538

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 19, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

PECONPI: a novel software for uncovering pathogenic copy number variations in non-syndromic sensorineural hearing loss and other genetically heterogeneous disorders.

Tsai EA, Berman MA, Conlin LK, Rehm HL, Francey LJ, Deardorff MA, Holst J, Kaur M, Gallant E, Clark DM, Glessner JT, Jensen ST, Grant SF, Gruber PJ, Hakonarson H, Spinner NB, Krantz ID.

Am J Med Genet A. 2013 Sep;161A(9):2134-47. doi: 10.1002/ajmg.a.36038. Epub 2013 Jul 29.

PubMed [citation]

PMID:: 23897863
PMCID:: PMC3745548

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

See all PubMed Citations (3)

Details of each submission

From Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV002009998.3

#	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	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002222419.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 417 of the OTOA protein (p.Leu417Phe). This variant is present in population databases (rs764182550, gnomAD 0.004%). This missense change has been observed in individual(s) with deafness (PMID: 23897863). ClinVar contains an entry for this variant (Variation ID: 1319143). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV004227538.1

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

Description

PP1, PM2, PM3

#	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		1	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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