NM_032578.4(MYPN):c.3136A>C (p.Thr1046Pro) AND Dilated cardiomyopathy 1KK

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 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:: RCV001212270.4

Allele description

NM_032578.4(MYPN):c.3136A>C (p.Thr1046Pro)

Gene:

MYPN:myopalladin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q21.3

Genomic location:

Preferred name:

NM_032578.4(MYPN):c.3136A>C (p.Thr1046Pro)

HGVS:

NC_000010.11:g.68195510A>C
NG_032118.1:g.94394A>C
NM_001256267.2:c.3136A>C
NM_001256268.2:c.2254A>C
NM_032578.4:c.3136A>CMANE SELECT
NP_001243196.1:p.Thr1046Pro
NP_001243197.1:p.Thr752Pro
NP_115967.2:p.Thr1046Pro
LRG_410t1:c.3136A>C
LRG_410:g.94394A>C
NC_000010.10:g.69955267A>C
NM_032578.2:c.3136A>C
NM_032578.3:c.3136A>C
NM_032578.4:c.3136A>C
NR_045662.4:n.2673A>C
NR_045663.4:n.3210A>C

Protein change:

T1046P

Links:

dbSNP: rs374007615

NCBI 1000 Genomes Browser:

rs374007615

Molecular consequence:

NM_001256267.2:c.3136A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001256268.2:c.2254A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_032578.4:c.3136A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_045662.4:n.2673A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_045663.4:n.3210A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Dilated cardiomyopathy 1KK (CMD1KK)
Identifiers:: MONDO: MONDO:0014100; MedGen: C3714995; Orphanet: 154; Orphanet: 75249; OMIM: 615248

Recent activity

Clear Turn Off Turn On

acyltransferase, partial [Mesorhizobium loti]
acyltransferase, partial [Mesorhizobium loti]
gi|321689049|gb|ADW94991.1|

Protein
nh88d05.s1 NCI_CGAP_Br1.1 Homo sapiens cDNA clone IMAGE:965577 3', mRNA sequence
nh88d05.s1 NCI_CGAP_Br1.1 Homo sapiens cDNA clone IMAGE:965577 3', mRNA sequence
gi|2252149|gnl|dbEST|1158377|gb|AA5 .1|

Nucleotide

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
SCV001383850	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 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

SCV001383850

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 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 Invitae, SCV001383850.4

#	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 threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1046 of the MYPN protein (p.Thr1046Pro). This variant is present in population databases (rs374007615, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MYPN-related conditions. ClinVar contains an entry for this variant (Variation ID: 942308). 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 tolerated. 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

Last Updated: Jul 29, 2024

ClinVar

Relating variation to medicine