NM_001005373.4(LRSAM1):c.1817G>A (p.Gly606Glu) AND Charcot-Marie-Tooth disease axonal type 2P

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 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:: RCV003642578.2

Allele description [Variation Report for NM_001005373.4(LRSAM1):c.1817G>A (p.Gly606Glu)]

NM_001005373.4(LRSAM1):c.1817G>A (p.Gly606Glu)

Gene:

LRSAM1:leucine rich repeat and sterile alpha motif containing 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

9q33.3

Genomic location:

Preferred name:

NM_001005373.4(LRSAM1):c.1817G>A (p.Gly606Glu)

HGVS:

NC_000009.12:g.127496082G>A
NG_032008.1:g.49597G>A
NM_001005373.4:c.1817G>AMANE SELECT
NM_001005374.4:c.1817G>A
NM_001190723.3:c.1736G>A
NM_001384142.1:c.1817G>A
NM_001384143.1:c.1718G>A
NM_001384144.1:c.1028G>A
NM_138361.5:c.1817G>A
NP_001005373.1:p.Gly606Glu
NP_001005374.1:p.Gly606Glu
NP_001177652.1:p.Gly579Glu
NP_001371071.1:p.Gly606Glu
NP_001371072.1:p.Gly573Glu
NP_001371073.1:p.Gly343Glu
NP_612370.3:p.Gly606Glu
LRG_373t1:c.1817G>A
LRG_373:g.49597G>A
LRG_373p1:p.Gly606Glu
NC_000009.11:g.130258361G>A
NR_168891.1:n.2346G>A
NR_168892.1:n.2170G>A

Protein change:

G343E

Molecular consequence:

NM_001005373.4:c.1817G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001005374.4:c.1817G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001190723.3:c.1736G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001384142.1:c.1817G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001384143.1:c.1718G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001384144.1:c.1028G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_138361.5:c.1817G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_168891.1:n.2346G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_168892.1:n.2170G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Charcot-Marie-Tooth disease axonal type 2P
Synonyms:: CHARCOT-MARIE-TOOTH NEUROPATHY, TYPE 2P; Charcot-Marie-Tooth disease type 2P; CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2G; See all synonyms [MedGen]
Identifiers:: Gene: 431712; MONDO: MONDO:0013753; MedGen: C3280797; Orphanet: 300319; Orphanet: 99941; OMIM: 614436

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004519072	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 22, 2023)	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

SCV004519072

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 22, 2023)

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, SCV004519072.1

#	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 glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 606 of the LRSAM1 protein (p.Gly606Glu). This variant is present in population databases (rs368858589, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with LRSAM1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LRSAM1 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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