NM_170707.4(LMNA):c.62T>C (p.Leu21Pro) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 8, 2020
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:: RCV001090180.4

Allele description [Variation Report for NM_170707.4(LMNA):c.62T>C (p.Leu21Pro)]

NM_170707.4(LMNA):c.62T>C (p.Leu21Pro)

Genes:

LOC129931597:ATAC-STARR-seq lymphoblastoid silent region 1421 [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.62T>C (p.Leu21Pro)

HGVS:

NC_000001.11:g.156114980T>C
NG_008692.2:g.37408T>C
NM_001282625.2:c.62T>C
NM_001282626.2:c.62T>C
NM_005572.4:c.62T>C
NM_170707.4:c.62T>CMANE SELECT
NM_170708.4:c.62T>C
NP_001269554.1:p.Leu21Pro
NP_001269555.1:p.Leu21Pro
NP_005563.1:p.Leu21Pro
NP_733821.1:p.Leu21Pro
NP_733822.1:p.Leu21Pro
LRG_254:g.37408T>C
NC_000001.10:g.156084771T>C
NC_000001.10:g.156084771T>C

Protein change:

L21P

Links:

dbSNP: rs1649704361

NCBI 1000 Genomes Browser:

rs1649704361

Molecular consequence:

NM_001282625.2:c.62T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282626.2:c.62T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_005572.4:c.62T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_170707.4:c.62T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_170708.4:c.62T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Developmental regression
Synonyms:: C1836830
Identifiers:: MedGen: C1836830; Human Phenotype Ontology: HP:0002376

Name:: Relative macrocephaly
Identifiers:: MedGen: C1849075; Human Phenotype Ontology: HP:0004482

Name:: Severe muscular hypotonia
Identifiers:: MedGen: C1839630; Human Phenotype Ontology: HP:0006829

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001244297	Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 8, 2020)	unknown	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

SCV001244297

Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 8, 2020)

unknown

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	unknown	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 Diagnostics Services (NGS), CSIR - Centre For Cellular And Molecular Biology, SCV001244297.1

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

Description

Homozygous or compound heterozygous variations in LMNA gene (MIM*150330) are known to cause various developmental growth retardation related disorders (MIM#605588; 616516; 176670; 248370; 275210). The c.62T>C variant is not present in publicly available databases like 1000 Genomes, EVS, ExAC, gnomAD and dbSNP. The variant is not present in our in-house exome database. The variant was not reported to OMIM, HGMD or ClinVar databases in any affected individuals. Predictions from different in-silico pathogenicity prediction programs like SIFT, PolyPhen-3, MutationTaster2, CADD etc. are contradictory. There are no documented functional studies. Due to lack of enough evidence the variant has been classified as uncertain significance.

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

Last Updated: Sep 29, 2024

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