NM_004320.6(ATP2A1):c.1253C>T (p.Ala418Val) AND Brody myopathy

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 5, 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:: RCV001946341.9

Allele description [Variation Report for NM_004320.6(ATP2A1):c.1253C>T (p.Ala418Val)]

NM_004320.6(ATP2A1):c.1253C>T (p.Ala418Val)

Gene:

ATP2A1:ATPase sarcoplasmic/endoplasmic reticulum Ca2+ transporting 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p11.2

Genomic location:

Preferred name:

NM_004320.6(ATP2A1):c.1253C>T (p.Ala418Val)

HGVS:

NC_000016.10:g.28894573C>T
NG_023327.1:g.21086C>T
NM_001286075.2:c.878C>T
NM_004320.6:c.1253C>TMANE SELECT
NM_173201.4:c.1253C>T
NM_173201.5:c.1253C>T
NP_001273004.1:p.Ala293Val
NP_004311.1:p.Ala418Val
NP_775293.1:p.Ala418Val
NC_000016.9:g.28905894C>T

Protein change:

A293V

Links:

dbSNP: rs2152209408

NCBI 1000 Genomes Browser:

rs2152209408

Molecular consequence:

NM_001286075.2:c.878C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004320.6:c.1253C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_173201.5:c.1253C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Brody myopathy
Synonyms:: BRODY DISEASE
Identifiers:: MONDO: MONDO:0010977; MedGen: C1832918; Orphanet: 53347; OMIM: 601003

Recent activity

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Homo sapiens granzyme M (GZMM), transcript variant 2, mRNA
Homo sapiens granzyme M (GZMM), transcript variant 2, mRNA
gi|1676318782|ref|NM_001258351.2|

Nucleotide
Homo sapiens cDNA FLJ57465 complete cds
Homo sapiens cDNA FLJ57465 complete cds
gi|194382745|dbj|AK303513.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002214054	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 5, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003834357	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 5, 2021)	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

SCV002214054

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 5, 2022)

germline

clinical testing

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

SCV003834357

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 5, 2021)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002214054.3

#	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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1434504). This variant has not been reported in the literature in individuals affected with ATP2A1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 418 of the ATP2A1 protein (p.Ala418Val).

#	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, SCV003834357.2

#	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: Sep 29, 2024

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