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NM_001005373.4(LRSAM1):c.2120C>G (p.Pro707Arg) AND Charcot-Marie-Tooth disease axonal type 2P

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 16, 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:
RCV003644424.2

Allele description [Variation Report for NM_001005373.4(LRSAM1):c.2120C>G (p.Pro707Arg)]

NM_001005373.4(LRSAM1):c.2120C>G (p.Pro707Arg)

Gene:
LRSAM1:leucine rich repeat and sterile alpha motif containing 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_001005373.4(LRSAM1):c.2120C>G (p.Pro707Arg)
HGVS:
  • NC_000009.12:g.127502847C>G
  • NG_032008.1:g.56362C>G
  • NM_001005373.4:c.2120C>GMANE SELECT
  • NM_001005374.4:c.2120C>G
  • NM_001190723.3:c.2039C>G
  • NM_001384142.1:c.2120C>G
  • NM_001384143.1:c.2021C>G
  • NM_001384144.1:c.1331C>G
  • NM_138361.5:c.2120C>G
  • NP_001005373.1:p.Pro707Arg
  • NP_001005374.1:p.Pro707Arg
  • NP_001177652.1:p.Pro680Arg
  • NP_001371071.1:p.Pro707Arg
  • NP_001371072.1:p.Pro674Arg
  • NP_001371073.1:p.Pro444Arg
  • NP_612370.3:p.Pro707Arg
  • LRG_373t1:c.2120C>G
  • LRG_373:g.56362C>G
  • LRG_373p1:p.Pro707Arg
  • NC_000009.11:g.130265126C>G
  • NR_168891.1:n.2649C>G
  • NR_168892.1:n.2473C>G
Protein change:
P444R
Molecular consequence:
  • NM_001005373.4:c.2120C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001005374.4:c.2120C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001190723.3:c.2039C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384142.1:c.2120C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384143.1:c.2021C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384144.1:c.1331C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_138361.5:c.2120C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_168891.1:n.2649C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_168892.1:n.2473C>G - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004465373Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(May 16, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

LRSAM1-mediated ubiquitylation is disrupted in axonal Charcot-Marie-Tooth disease 2P.

Hakonen JE, Sorrentino V, Avagliano Trezza R, de Wissel MB, van den Berg M, Bleijlevens B, van Ruissen F, Distel B, Baas F, Zelcer N, Weterman MAJ.

Hum Mol Genet. 2017 Jun 1;26(11):2034-2041. doi: 10.1093/hmg/ddx089.

PubMed [citation]
PMID:
28335037

Comprehensive genetic sequence and copy number analysis for Charcot-Marie-Tooth disease in a Canadian cohort of 2517 patients.

Volodarsky M, Kerkhof J, Stuart A, Levy M, Brady LI, Tarnopolsky M, Lin H, Ainsworth P, Sadikovic B.

J Med Genet. 2021 Apr;58(4):284-288. doi: 10.1136/jmedgenet-2019-106641. Epub 2020 May 6.

PubMed [citation]
PMID:
32376792
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004465373.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

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. This variant disrupts the p.Pro707 amino acid residue in LRSAM1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28335037, 32376792). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt LRSAM1 protein function. This variant has not been reported in the literature in individuals affected with LRSAM1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 707 of the LRSAM1 protein (p.Pro707Arg).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024