NM_001142800.2(EYS):c.4991C>T (p.Thr1664Ile) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Oct 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:: RCV001245603.5

Allele description [Variation Report for NM_001142800.2(EYS):c.4991C>T (p.Thr1664Ile)]

NM_001142800.2(EYS):c.4991C>T (p.Thr1664Ile)

Gene:

EYS:eyes shut homolog [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q12

Genomic location:

Preferred name:

NM_001142800.2(EYS):c.4991C>T (p.Thr1664Ile)

HGVS:

NC_000006.12:g.64590876G>A
NG_023443.2:g.1121350C>T
NM_001142800.2:c.4991C>TMANE SELECT
NM_001292009.2:c.4991C>T
NP_001136272.1:p.Thr1664Ile
NP_001278938.1:p.Thr1664Ile
FM209056.1:c.4991C>T
NC_000006.11:g.65300769G>A
NM_001142800.1:c.4991C>T

Protein change:

T1664I

Links:

dbSNP: rs561830314

NCBI 1000 Genomes Browser:

rs561830314

Molecular consequence:

NM_001142800.2:c.4991C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001292009.2:c.4991C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001418901	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 20333770, 28492532
SCV001848816	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Benign (Mar 3, 2015)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001418901

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2022)

germline

clinical testing

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

SCV001848816

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Benign
(Mar 3, 2015)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

EYS is a major gene for rod-cone dystrophies in France.

Audo I, Sahel JA, Mohand-Saïd S, Lancelot ME, Antonio A, Moskova-Doumanova V, Nandrot EF, Doumanov J, Barragan I, Antinolo G, Bhattacharya SS, Zeitz C.

Hum Mutat. 2010 May;31(5):E1406-35. doi: 10.1002/humu.21249.

PubMed [citation]

PMID:: 20333770

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001418901.3

#	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 threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1664 of the EYS protein (p.Thr1664Ile). This variant is present in population databases (rs561830314, gnomAD 0.06%). This missense change has been observed in individuals with clinical features of retinitis pigmentosa (PMID: 20333770; Invitae). ClinVar contains an entry for this variant (Variation ID: 911905). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 GeneDx, SCV001848816.1

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

#	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: Feb 4, 2024

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