NM_020366.4(RPGRIP1):c.1945C>A (p.Gln649Lys) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 12, 2022
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:: RCV001922690.6

Allele description [Variation Report for NM_020366.4(RPGRIP1):c.1945C>A (p.Gln649Lys)]

NM_020366.4(RPGRIP1):c.1945C>A (p.Gln649Lys)

Gene:

RPGRIP1:RPGR interacting protein 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q11.2

Genomic location:

Preferred name:

NM_020366.4(RPGRIP1):c.1945C>A (p.Gln649Lys)

HGVS:

NC_000014.9:g.21324800C>A
NG_008933.1:g.41824C>A
NM_001377523.1:c.688+2796C>A
NM_001377948.1:c.871C>A
NM_001377949.1:c.796+75C>A
NM_001377950.1:c.688+2796C>A
NM_001377951.1:c.190+2796C>A
NM_020366.4:c.1945C>AMANE SELECT
NP_001364877.1:p.Gln291Lys
NP_065099.3:p.Gln649Lys
NC_000014.8:g.21792959C>A

Protein change:

Q291K

Links:

dbSNP: rs747575530

NCBI 1000 Genomes Browser:

rs747575530

Molecular consequence:

NM_001377523.1:c.688+2796C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001377949.1:c.796+75C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001377950.1:c.688+2796C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001377951.1:c.190+2796C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001377948.1:c.871C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_020366.4:c.1945C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cone-rod dystrophy 13 (CORD13)
Identifiers:: MONDO: MONDO:0011987; MedGen: C2750720; Orphanet: 1872; OMIM: 608194

Name:: Leber congenital amaurosis 6 (LCA6)
Identifiers:: MONDO: MONDO:0013446; MedGen: C1854260; Orphanet: 65; OMIM: 613826

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002167503	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 12, 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

SCV002167503

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 12, 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002167503.3

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

Description

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. 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 lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1398945). This missense change has been observed in individual(s) with clincal features of inherited retinal dystrophy (Invitae). This variant is present in population databases (rs747575530, gnomAD 0.0009%). This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 649 of the RPGRIP1 protein (p.Gln649Lys).

#	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: Sep 29, 2024

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