NM_173477.5(USH1G):c.1258C>G (p.Leu420Val) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 21, 2016
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:: RCV000041414.8

Allele description [Variation Report for NM_173477.5(USH1G):c.1258C>G (p.Leu420Val)]

NM_173477.5(USH1G):c.1258C>G (p.Leu420Val)

Gene:

USH1G:USH1 protein network component sans [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q25.1

Genomic location:

Preferred name:

NM_173477.5(USH1G):c.1258C>G (p.Leu420Val)

HGVS:

NC_000017.11:g.74919578G>C
NG_007882.2:g.8686C>G
NG_033062.2:g.304G>C
NM_001282489.3:c.949C>G
NM_173477.5:c.1258C>GMANE SELECT
NP_001269418.1:p.Leu317Val
NP_775748.2:p.Leu420Val
LRG_1416t1:c.1258C>G
LRG_1416:g.8686C>G
LRG_1416p1:p.Leu420Val
NC_000017.10:g.72915673G>C
NG_033062.1:g.304G>C
NM_173477.2:c.1258C>G
NM_173477.4:c.1258C>G
c.1258C>G

Protein change:

L317V

Links:

dbSNP: rs139897506

NCBI 1000 Genomes Browser:

rs139897506

Molecular consequence:

NM_001282489.3:c.949C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_173477.5:c.1258C>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
SCV000065109	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Jul 21, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23591405, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000065109

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Jul 21, 2016)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	5	5	not provided	not provided	not provided	clinical testing

Citations

PubMed

Panel-based next generation sequencing as a reliable and efficient technique to detect mutations in unselected patients with retinal dystrophies.

Glöckle N, Kohl S, Mohr J, Scheurenbrand T, Sprecher A, Weisschuh N, Bernd A, Rudolph G, Schubach M, Poloschek C, Zrenner E, Biskup S, Berger W, Wissinger B, Neidhardt J.

Eur J Hum Genet. 2014 Jan;22(1):99-104. doi: 10.1038/ejhg.2013.72. Epub 2013 Apr 17.

PubMed [citation]

PMID:: 23591405
PMCID:: PMC3865404

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, SCV000065109.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	PubMed (2)

Description

Variant classified as Uncertain Significance - Favor Benign. The p.Leu420Val var iant in USH1G has now been identified in 2 individuals with Usher syndrome and 5 individuals with hearing loss. One of the individuals with Usher syndrome had t wo pathogenic variants in another gene which explained the disease (Glockle 2014 ). A variant affecting the remaining copy of USH1G was not detected in any of th e other individuals (LMM data). This variant has been identified in 0.2% (109/62 876) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://e xac.broadinstitute.org; dbSNP rs139897506). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathog enic role. Computational prediction tools and conservation analyses do not provi de strong support for or against an impact to the protein. In summary, while the clinical significance of the p.Leu420Val variant is uncertain, these data sugge st that it is more likely to be benign.

#	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		5	not provided	5	not provided

Last Updated: Oct 26, 2024

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