U.S. flag

An official website of the United States government

NM_003640.5(ELP1):c.2741C>T (p.Pro914Leu) AND Familial dysautonomia

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Jan 7, 2021
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:
RCV000006460.4

Allele description [Variation Report for NM_003640.5(ELP1):c.2741C>T (p.Pro914Leu)]

NM_003640.5(ELP1):c.2741C>T (p.Pro914Leu)

Gene:
ELP1:elongator acetyltransferase complex subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q31.3
Genomic location:
Preferred name:
NM_003640.5(ELP1):c.2741C>T (p.Pro914Leu)
HGVS:
  • NC_000009.12:g.108894062G>A
  • NG_008788.1:g.45267C>T
  • NM_001318360.2:c.2399C>T
  • NM_001330749.2:c.1694C>T
  • NM_003640.5:c.2741C>TMANE SELECT
  • NP_001305289.1:p.Pro800Leu
  • NP_001317678.1:p.Pro565Leu
  • NP_003631.2:p.Pro914Leu
  • LRG_251:g.45267C>T
  • NC_000009.11:g.111656342G>A
  • NM_003640.3:c.2741C>T
  • NM_003640.4:c.2741C>T
  • c.2741C>T (p.Pro914Leu)
Protein change:
P565L; PRO914LEU
Links:
OMIM: 603722.0003; dbSNP: rs28939712
NCBI 1000 Genomes Browser:
rs28939712
Molecular consequence:
  • NM_001318360.2:c.2399C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001330749.2:c.1694C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003640.5:c.2741C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial dysautonomia (HSAN3)
Synonyms:
NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE III; HSAN III; Hereditary sensory and autonomic neuropathy 3; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009131; MedGen: C0013364; Orphanet: 1764; OMIM: 223900

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000026643OMIM
no assertion criteria provided
Pathogenic
(May 1, 2003)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

SCV001478676Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Likely pathogenic
(Jan 7, 2021)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Precise genetic mapping and haplotype analysis of the familial dysautonomia gene on human chromosome 9q31.

Blumenfeld A, Slaugenhaupt SA, Liebert CB, Temper V, Maayan C, Gill S, Lucente DE, Idelson M, MacCormack K, Monahan MA, Mull J, Leyne M, Mendillo M, Schiripo T, Mishori E, Breakefield X, Axelrod FB, Gusella JF.

Am J Hum Genet. 1999 Apr;64(4):1110-8.

PubMed [citation]
PMID:
10090896
PMCID:
PMC1377835

An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals.

Lazarin GA, Haque IS, Nazareth S, Iori K, Patterson AS, Jacobson JL, Marshall JR, Seltzer WK, Patrizio P, Evans EA, Srinivasan BS.

Genet Med. 2013 Mar;15(3):178-86. doi: 10.1038/gim.2012.114. Epub 2012 Sep 13.

PubMed [citation]
PMID:
22975760
PMCID:
PMC3908551
See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000026643.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a patient with familial dysautonomia (223900), previously reported by Blumenfeld et al. (1999), Leyne et al. (2003) identified compound heterozygosity for the major FD haplotype (603722.0001), which was inherited from the Ashkenazi Jewish father, and a 3051C-T transition in exon 26 of the IKBKAP gene, resulting in a pro914-to-leu (P914L) substitution, from the mother, who was of Irish-German/Sicilian heritage. The patient fulfilled all diagnostic criteria for FD other than pure Ashkenazi Jewish ancestry.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001478676.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

Variant summary: IKBKAP c.2741C>T (p.Pro914Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 242538 control chromosomes (gnomAD). c.2741C>T has been reported in the literature in at least one compound heterozygous individual affected with Familial Dysautonomia (e.g. Leyne_2003). This patient, the first non-Ashkenazi Jewish individual reported with this disorder, has been cited multiple times in subsequent publications (e.g. Gold-von Simson_2008, Monaghan_2008, Rubin_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Jan 13, 2025