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NM_001005373.4(LRSAM1):c.2033_2038del (p.Cys678_Glu680delinsTer) AND Charcot-Marie-Tooth disease axonal type 2P

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 29, 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:
RCV003644089.2

Allele description [Variation Report for NM_001005373.4(LRSAM1):c.2033_2038del (p.Cys678_Glu680delinsTer)]

NM_001005373.4(LRSAM1):c.2033_2038del (p.Cys678_Glu680delinsTer)

Gene:
LRSAM1:leucine rich repeat and sterile alpha motif containing 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
9q34.11
Genomic location:
Preferred name:
NM_001005373.4(LRSAM1):c.2033_2038del (p.Cys678_Glu680delinsTer)
HGVS:
  • NC_000009.12:g.127501130_127501135del
  • NG_032008.1:g.54645_54650del
  • NG_117561.1:g.661_666del
  • NM_001005373.4:c.2033_2038delMANE SELECT
  • NM_001005374.4:c.2033_2038del
  • NM_001190723.3:c.1952_1957del
  • NM_001384142.1:c.2033_2038del
  • NM_001384143.1:c.1934_1939del
  • NM_001384144.1:c.1244_1249del
  • NM_138361.5:c.2033_2038del
  • NP_001005373.1:p.Cys678_Glu680delinsTer
  • NP_001005374.1:p.Cys678_Glu680delinsTer
  • NP_001177652.1:p.Cys651_Glu653delinsTer
  • NP_001371071.1:p.Cys678_Glu680delinsTer
  • NP_001371072.1:p.Cys645_Glu647delinsTer
  • NP_001371073.1:p.Cys415_Glu417delinsTer
  • NP_612370.3:p.Cys678_Glu680delinsTer
  • LRG_373t1:c.2033_2038del
  • LRG_373:g.54645_54650del
  • LRG_373p1:p.Cys678_Glu680delinsTer
  • NC_000009.11:g.130263409_130263414del
  • NR_168891.1:n.2562_2567del
  • NR_168892.1:n.2386_2391del
Molecular consequence:
  • NR_168891.1:n.2562_2567del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_168892.1:n.2386_2391del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001005373.4:c.2033_2038del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001005374.4:c.2033_2038del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001190723.3:c.1952_1957del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001384142.1:c.2033_2038del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001384143.1:c.1934_1939del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001384144.1:c.1244_1249del - nonsense - [Sequence Ontology: SO:0001587]
  • NM_138361.5:c.2033_2038del - nonsense - [Sequence Ontology: SO:0001587]

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
SCV004499739Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Apr 29, 2023) 		germlineclinical testing

PubMed (4)
[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

Location matters - Genotype-phenotype correlation in LRSAM1 mutations associated with rare Charcot-Marie-Tooth neuropathy CMT2P.

Reilich P, Schlotter B, Montagnese F, Jordan B, Stock F, Schäff-Vogelsang M, Hotter B, Eger K, Diebold I, Erdmann H, Becker K, Schön U, Abicht A.

Neuromuscul Disord. 2021 Feb;31(2):123-133. doi: 10.1016/j.nmd.2020.11.011. Epub 2020 Nov 28.

PubMed [citation]
PMID:
33414056

Mutation spectrum of Charcot-Marie-Tooth disease among the Han Chinese in Taiwan.

Hsu YH, Lin KP, Guo YC, Tsai YS, Liao YC, Lee YC.

Ann Clin Transl Neurol. 2019 Jun;6(6):1090-1101. doi: 10.1002/acn3.50797.

PubMed [citation]
PMID:
31211173
PMCID:
PMC6562034
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004499739.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This protein change is located in a region of the LRSAM1 protein where a significant number of LRSAM1 nonsense and frameshift mutations have been reported in autosomal dominant Charcot-Marie-Tooth disease (PMID: 33414056, 31211173, 29341362). 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 creates a premature translational stop signal (p.Cys678*) in the LRSAM1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 46 amino acid(s) of the LRSAM1 protein.

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

Last Updated: Sep 29, 2024