NM_001105206.3(LAMA4):c.188C>T (p.Ala63Val) AND Dilated cardiomyopathy 1JJ

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 20, 2024
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:: RCV001362930.7

Allele description [Variation Report for NM_001105206.3(LAMA4):c.188C>T (p.Ala63Val)]

NM_001105206.3(LAMA4):c.188C>T (p.Ala63Val)

Genes:

LAMA4-AS1:LAMA4 antisense RNA 1 [Gene - HGNC]
LAMA4:laminin subunit alpha 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q21

Genomic location:

Preferred name:

NM_001105206.3(LAMA4):c.188C>T (p.Ala63Val)

HGVS:

NC_000006.12:g.112253963G>A
NG_008209.1:g.5664C>T
NM_001105206.3:c.188C>TMANE SELECT
NM_001105207.3:c.188C>T
NM_001105208.3:c.188C>T
NM_001105209.3:c.188C>T
NM_002290.3:c.188C>T
NM_002290.5:c.188C>T
NP_001098676.2:p.Ala63Val
NP_001098677.2:p.Ala63Val
NP_001098678.1:p.Ala63Val
NP_001098679.1:p.Ala63Val
NP_002281.3:p.Ala63Val
LRG_433t2:c.188C>T
LRG_433:g.5664C>T
NC_000006.11:g.112575165G>A
NM_001105209.2:c.188C>T

Protein change:

A63V

Links:

dbSNP: rs370868386

NCBI 1000 Genomes Browser:

rs370868386

Molecular consequence:

NM_001105206.3:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001105207.3:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001105208.3:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001105209.3:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002290.5:c.188C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dilated cardiomyopathy 1JJ (CMD1JJ)
Identifiers:: MONDO: MONDO:0014095; MedGen: C3808935; Orphanet: 154; OMIM: 615235

Recent activity

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shoot+N_mRNA, Rep2
shoot+N_mRNA, Rep2

biosample
MULTISPECIES: alkyl hydroperoxide reductase subunit C [Pseudoalteromonas]
MULTISPECIES: alkyl hydroperoxide reductase subunit C [Pseudoalteromonas]
gi|490724572|ref|WP_004587118.1|

Protein
HELO_RS19360 [Halomonas elongata DSM 2581]
HELO_RS19360 [Halomonas elongata DSM 2581]
Gene ID:91011982

Gene
HELO_RS19435 [Halomonas elongata DSM 2581]
HELO_RS19435 [Halomonas elongata DSM 2581]
Gene ID:91011993

Gene
HELO_RS19410 [Halomonas elongata DSM 2581]
HELO_RS19410 [Halomonas elongata DSM 2581]
Gene ID:91011988

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001558990	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 20, 2024)	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

SCV001558990

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 20, 2024)

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001558990.4

#	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 alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 63 of the LAMA4 protein (p.Ala63Val). This variant is present in population databases (rs370868386, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 978755). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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: Sep 29, 2024

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