NM_170707.4(LMNA):c.749C>T (p.Ala250Val) AND Cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 22, 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:: RCV001186222.4

Allele description [Variation Report for NM_170707.4(LMNA):c.749C>T (p.Ala250Val)]

NM_170707.4(LMNA):c.749C>T (p.Ala250Val)

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.749C>T (p.Ala250Val)

HGVS:

NC_000001.11:g.156134914C>T
NG_008692.2:g.57342C>T
NM_001257374.3:c.413C>T
NM_001282624.2:c.506C>T
NM_001282625.2:c.749C>T
NM_001282626.2:c.749C>T
NM_005572.4:c.749C>T
NM_170707.4:c.749C>TMANE SELECT
NM_170708.4:c.749C>T
NP_001244303.1:p.Ala138Val
NP_001269553.1:p.Ala169Val
NP_001269554.1:p.Ala250Val
NP_001269555.1:p.Ala250Val
NP_005563.1:p.Ala250Val
NP_005563.1:p.Ala250Val
NP_733821.1:p.Ala250Val
NP_733822.1:p.Ala250Val
LRG_254t1:c.749C>T
LRG_254t2:c.749C>T
LRG_254:g.57342C>T
LRG_254p1:p.Ala250Val
NC_000001.10:g.156104705C>T
NM_005572.3:c.749C>T
NM_170707.2:c.749C>T
NM_170707.3:c.749C>T
c.749C>T

Protein change:

A138V

Links:

dbSNP: rs397517907

NCBI 1000 Genomes Browser:

rs397517907

Molecular consequence:

NM_001257374.3:c.413C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.506C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.749C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.749C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.749C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.749C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.749C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Homo sapiens isolate CHM13 chromosome 20, alternate assembly T2T-CHM13v2.0
Homo sapiens isolate CHM13 chromosome 20, alternate assembly T2T-CHM13v2.0
gi|2194972764|gnl|ASM:GCF_009914825 ef|NC_060944.1||gpp|GPC_000012759.1||gnl|NCBI_GENOMES|119580

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001352588	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jun 22, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 32041611, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001352588

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jun 22, 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

Six years' experience with LipidSeq: clinical and research learnings from a hybrid, targeted sequencing panel for dyslipidemias.

Dron JS, Wang J, McIntyre AD, Iacocca MA, Robinson JF, Ban MR, Cao H, Hegele RA.

BMC Med Genomics. 2020 Feb 10;13(1):23. doi: 10.1186/s12920-020-0669-2.

PubMed [citation]

PMID:: 32041611
PMCID:: PMC7011550

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, SCV001352588.3

#	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 alanine with valine at codon 250 of the LMNA protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with dyslipidemia (PMID: 32041611). This variant has been identified in 1/251422 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: Sep 29, 2024

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