NM_006258.4(PRKG1):c.319G>C (p.Asp107His) AND Aortic aneurysm, familial thoracic 8

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Sep 3, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000535981.9

Allele description

NM_006258.4(PRKG1):c.319G>C (p.Asp107His)

Gene:

PRKG1:protein kinase cGMP-dependent 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q21.1

Genomic location:

Preferred name:

NM_006258.4(PRKG1):c.319G>C (p.Asp107His)

HGVS:

NC_000010.11:g.51153171G>C
NG_029982.1:g.167021G>C
NM_001098512.3:c.274G>C
NM_006258.4:c.319G>CMANE SELECT
NP_001091982.1:p.Asp92His
NP_006249.1:p.Asp107His
LRG_1135t1:c.319G>C
LRG_1135t2:c.274G>C
LRG_1135:g.167021G>C
LRG_1135p1:p.Asp107His
LRG_1135p2:p.Asp92His
NC_000010.10:g.52912931G>C
NM_006258.3:c.319G>C

Protein change:

D107H

Links:

dbSNP: rs751916382

NCBI 1000 Genomes Browser:

rs751916382

Molecular consequence:

NM_001098512.3:c.274G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_006258.4:c.319G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Aortic aneurysm, familial thoracic 8 (AAT8)
Identifiers:: MONDO: MONDO:0014187; MedGen: C3809513; OMIM: 615436

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000659233	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 27, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003809886	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 3, 2019)	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

SCV000659233

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 27, 2017)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003809886

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 3, 2019)

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Invitae, SCV000659233.4

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

Description

This sequence change replaces aspartic acid with histidine at codon 107 of the PRKG1 protein (p.Asp107His). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is present in population databases (rs751916382, ExAC 0.01%) but has not been reported in the literature in individuals with a PRKG1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 Revvity Omics, Revvity, SCV003809886.2

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

#	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: May 19, 2024

ClinVar

Relating variation to medicine