NM_002863.5(PYGL):c.1454A>G (p.Asn485Ser) AND Glycogen storage disease, type VI

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Mar 16, 2022
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:: RCV001043719.7

Allele description [Variation Report for NM_002863.5(PYGL):c.1454A>G (p.Asn485Ser)]

NM_002863.5(PYGL):c.1454A>G (p.Asn485Ser)

Gene:

PYGL:glycogen phosphorylase L [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q22.1

Genomic location:

Preferred name:

NM_002863.5(PYGL):c.1454A>G (p.Asn485Ser)

HGVS:

NC_000014.9:g.50914765T>C
NG_012796.1:g.34766A>G
NM_001163940.2:c.1352A>G
NM_002863.5:c.1454A>GMANE SELECT
NP_001157412.1:p.Asn451Ser
NP_002854.3:p.Asn485Ser
NC_000014.8:g.51381483T>C
NM_002863.4:c.1454A>G

Protein change:

N451S

Links:

dbSNP: rs138888959

NCBI 1000 Genomes Browser:

rs138888959

Molecular consequence:

NM_001163940.2:c.1352A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002863.5:c.1454A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Glycogen storage disease, type VI (GSD6)
Synonyms:: GSD VI; Glycogen storage disease type 6; Hers disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009294; MedGen: C0017925; Orphanet: 369; OMIM: 232700

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
SCV001207479	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002777827	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 16, 2022)	unknown	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

SCV001207479

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2021)

germline

clinical testing

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

SCV002777827

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 16, 2022)

unknown

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
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):240-242.

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, SCV001207479.4

#	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 asparagine with serine at codon 485 of the PYGL protein (p.Asn485Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs138888959, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with PYGL-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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 Fulgent Genetics, Fulgent Genetics, SCV002777827.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 7, 2023

ClinVar

Relating variation to medicine