NM_003322.6(TULP1):c.1466A>G (p.Lys489Arg) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 6, 2024
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:: RCV000086069.5

Allele description [Variation Report for NM_003322.6(TULP1):c.1466A>G (p.Lys489Arg)]

NM_003322.6(TULP1):c.1466A>G (p.Lys489Arg)

Gene:

TULP1:TUB like protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.31

Genomic location:

Preferred name:

NM_003322.6(TULP1):c.1466A>G (p.Lys489Arg)

HGVS:

NC_000006.12:g.35500010T>C
NG_009077.1:g.17861A>G
NM_001289395.2:c.1307A>G
NM_003322.6:c.1466A>GMANE SELECT
NP_001276324.1:p.Lys436Arg
NP_003313.3:p.Lys489Arg
NC_000006.11:g.35467787T>C
NM_003322.3:c.1466A>G
O00294:p.Lys489Arg

Protein change:

K436R

Links:

UniProtKB: O00294#VAR_008280; dbSNP: rs62636511

NCBI 1000 Genomes Browser:

rs62636511

Molecular consequence:

NM_001289395.2:c.1307A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003322.6:c.1466A>G - 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
SCV000118213	Retina International	no classification provided	not provided	not provided	not provided
SCV002235581	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 6, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27440997, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000118213

Retina International

no classification provided

not provided

SCV002235581

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 6, 2024)

germline

clinical testing

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

Description

http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg19&id=RISN_TULP1:c.1466A>G: SCV000118213

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	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

Pathogenic mutations in TULP1 responsible for retinitis pigmentosa identified in consanguineous familial cases.

Ullah I, Kabir F, Iqbal M, Gottsch CB, Naeem MA, Assir MZ, Khan SN, Akram J, Riazuddin S, Ayyagari R, Hejtmancik JF, Riazuddin SA.

Mol Vis. 2016;22:797-815.

PubMed [citation]

PMID:: 27440997
PMCID:: PMC4947966

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 Retina International, SCV000118213.1

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

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002235581.3

#	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 lysine, which is basic and polar, with arginine, which is basic and polar, at codon 489 of the TULP1 protein (p.Lys489Arg). This variant is present in population databases (rs62636511, gnomAD 0.02%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 27440997). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 99663). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TULP1 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.

#	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

Last Updated: Nov 3, 2024

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