NM_170707.4(LMNA):c.1601C>G (p.Thr534Ser) AND Cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 8, 2023
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:: RCV001526170.3

Allele description [Variation Report for NM_170707.4(LMNA):c.1601C>G (p.Thr534Ser)]

NM_170707.4(LMNA):c.1601C>G (p.Thr534Ser)

Gene:

LMNA:lamin A/C [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q22

Genomic location:

Preferred name:

NM_170707.4(LMNA):c.1601C>G (p.Thr534Ser)

HGVS:

NC_000001.11:g.156137225C>G
NG_008692.2:g.59653C>G
NM_001257374.3:c.1265C>G
NM_001282624.2:c.1358C>G
NM_001282625.2:c.1601C>G
NM_001282626.2:c.1601C>G
NM_005572.4:c.1601C>G
NM_170707.4:c.1601C>GMANE SELECT
NM_170708.4:c.1601C>G
NP_001244303.1:p.Thr422Ser
NP_001269553.1:p.Thr453Ser
NP_001269554.1:p.Thr534Ser
NP_001269555.1:p.Thr534Ser
NP_005563.1:p.Thr534Ser
NP_733821.1:p.Thr534Ser
NP_733822.1:p.Thr534Ser
LRG_254t2:c.1601C>G
LRG_254:g.59653C>G
NC_000001.10:g.156107016C>G
NM_170707.2:c.1601C>G
NM_170707.3:c.1601C>G

Protein change:

T422S

Links:

dbSNP: rs144740174

NCBI 1000 Genomes Browser:

rs144740174

Molecular consequence:

NM_001257374.3:c.1265C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.1358C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.1601C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.1601C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.1601C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.1601C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.1601C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiomyopathy (CMYO)
Synonyms:: Cardiomyopathies
Identifiers:: MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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
SCV001736467	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 8, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28688748, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001736467

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 8, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Congenital muscular dystrophies in the UK population: Clinical and molecular spectrum of a large cohort diagnosed over a 12-year period.

Sframeli M, Sarkozy A, Bertoli M, Astrea G, Hudson J, Scoto M, Mein R, Yau M, Phadke R, Feng L, Sewry C, Fen ANS, Longman C, McCullagh G, Straub V, Robb S, Manzur A, Bushby K, Muntoni F.

Neuromuscul Disord. 2017 Sep;27(9):793-803. doi: 10.1016/j.nmd.2017.06.008. Epub 2017 Jun 16.

PubMed [citation]

PMID:: 28688748

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 Color Diagnostics, LLC DBA Color Health, SCV001736467.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This missense variant replaces threonine with serine at codon 534 of the lamin A/C proteins. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with congenital muscular dystrophy (PMID: 28688748). This variant has been identified in 1/198866 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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: Apr 20, 2024

ClinVar

Relating variation to medicine