NM_001042702.5(PJVK):c.1A>G (p.Met1Val) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 1, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001449750.4

Allele description [Variation Report for NM_001042702.5(PJVK):c.1A>G (p.Met1Val)]

NM_001042702.5(PJVK):c.1A>G (p.Met1Val)

Gene:

PJVK:pejvakin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001042702.5(PJVK):c.1A>G (p.Met1Val)

HGVS:

NC_000002.12:g.178453410A>G
NG_009053.1:g.2822T>C
NG_012186.1:g.6975A>G
NM_001042702.5:c.1A>GMANE SELECT
NM_001353775.2:c.31-21A>G
NM_001353776.2:c.127-21A>G
NM_001353777.1:c.-334-143A>G
NM_001353778.2:c.-456-21A>G
NM_001369912.1:c.1A>G
NP_001036167.1:p.Met1Val
NP_001356841.1:p.Met1Val
NC_000002.11:g.179318137A>G

Protein change:

M1V

Links:

dbSNP: rs1697832820

NCBI 1000 Genomes Browser:

rs1697832820

Molecular consequence:

NM_001042702.5:c.1A>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001369912.1:c.1A>G - initiator_codon_variant - [Sequence Ontology: SO:0001582]
NM_001353775.2:c.31-21A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001353776.2:c.127-21A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001353777.1:c.-334-143A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001353778.2:c.-456-21A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001042702.5:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001369912.1:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001653025	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Jun 1, 2020)	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

SCV001653025

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Jun 1, 2020)

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	unknown	2	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV001653025.2

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

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The p.Met1? variant in DFNB59 (aka PJVK) has been previously reported by our laboratory in an individual with hearing loss who had a pathogenic DFNB59 variant identified in trans. It was absent from large population studies. This variant affects the translation initiation start codon (ATG) and is therefore predicted to disrupt translation although a variety of outcomes (no protein synthesis or the activation of an upstream translation initiation codon) are possible. Of note, several isoforms of the DFNB59 gene exist, with a transcript of similar length and coding regions (NM_001353775.1) having an alternate initiation codon location. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PVS1_Supporting, 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		2	not provided	1	not provided

Last Updated: Dec 24, 2023

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