NM_170707.4(LMNA):c.1106T>C (p.Leu369Pro) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 2, 2015
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:: RCV000236658.1

Allele description [Variation Report for NM_170707.4(LMNA):c.1106T>C (p.Leu369Pro)]

NM_170707.4(LMNA):c.1106T>C (p.Leu369Pro)

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.1106T>C (p.Leu369Pro)

HGVS:

NC_000001.11:g.156136070T>C
NG_008692.2:g.58498T>C
NM_001257374.3:c.770T>C
NM_001282624.2:c.863T>C
NM_001282625.2:c.1106T>C
NM_001282626.2:c.1106T>C
NM_005572.4:c.1106T>C
NM_170707.4:c.1106T>CMANE SELECT
NM_170708.4:c.1106T>C
NP_001244303.1:p.Leu257Pro
NP_001269553.1:p.Leu288Pro
NP_001269554.1:p.Leu369Pro
NP_001269555.1:p.Leu369Pro
NP_005563.1:p.Leu369Pro
NP_733821.1:p.Leu369Pro
NP_733822.1:p.Leu369Pro
LRG_254t2:c.1106T>C
LRG_254:g.58498T>C
NC_000001.10:g.156105861T>C
NM_170707.2:c.1106T>C
c.1106T>C

Protein change:

L257P

Links:

dbSNP: rs397517886

NCBI 1000 Genomes Browser:

rs397517886

Molecular consequence:

NM_001257374.3:c.770T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282624.2:c.863T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282625.2:c.1106T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.1106T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.1106T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.1106T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.1106T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

Recent activity

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PREDICTED: Gallus gallus B-locus zinc finger protein 1 (BZFP1), transcript varia...
PREDICTED: Gallus gallus B-locus zinc finger protein 1 (BZFP1), transcript variant X2, mRNA
gi|1390076696|ref|XM_015294947.2|

Nucleotide
PREDICTED: Mus musculus PRAME like 38 (Pramel38), mRNA
PREDICTED: Mus musculus PRAME like 38 (Pramel38), mRNA
gi|568936435|ref|XM_006535305.1|

Nucleotide
SPAC12B10.01c, partial [Schizosaccharomyces pombe]
SPAC12B10.01c, partial [Schizosaccharomyces pombe]
gi|4056559|emb|CAA22594.1|

Protein
immunoglobulin heavy chain junction region, partial [Homo sapiens]
immunoglobulin heavy chain junction region, partial [Homo sapiens]
gb|MOL11535.1||gnl|TLS:KCIZ|M04810: 000000-BKB5G:1:2113:9905:15909_1

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000293083	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Sep 2, 2015)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000293083

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Sep 2, 2015)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000293083.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The L369P variant was previously reported in a patient with dilated cardiomyopathy; however, segregation studies were not completed (Pugh et al., 2014). It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The L369P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with LMNA-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. This substitution occurs at a position that is conserved across species; however, Proline has been observed in evolution. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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