NM_006415.4(SPTLC1):c.718C>T (p.Arg240Cys) AND Hereditary sensory and autonomic neuropathy type 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 14, 2022
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:
RCV001326648.6

Allele description [Variation Report for NM_006415.4(SPTLC1):c.718C>T (p.Arg240Cys)]

NM_006415.4(SPTLC1):c.718C>T (p.Arg240Cys)

Gene:
SPTLC1:serine palmitoyltransferase long chain base subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q22.31
Genomic location:
Preferred name:
NM_006415.4(SPTLC1):c.718C>T (p.Arg240Cys)
HGVS:
  • NC_000009.12:g.92055467G>A
  • NG_007950.1:g.64942C>T
  • NM_001281303.2:c.718C>T
  • NM_001368272.1:c.352C>T
  • NM_001368273.1:c.253C>T
  • NM_006415.4:c.718C>TMANE SELECT
  • NP_001268232.1:p.Arg240Cys
  • NP_001355201.1:p.Arg118Cys
  • NP_001355202.1:p.Arg85Cys
  • NP_006406.1:p.Arg240Cys
  • LRG_272t1:c.718C>T
  • LRG_272:g.64942C>T
  • NC_000009.11:g.94817749G>A
  • NM_006415.2:c.718C>T
Protein change:
R118C
Links:
dbSNP: rs769908505
NCBI 1000 Genomes Browser:
rs769908505
Molecular consequence:
  • NM_001281303.2:c.718C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368272.1:c.352C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368273.1:c.253C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006415.4:c.718C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary sensory and autonomic neuropathy type 1 (HSAN1)
Synonyms:
HSAN 1; Neuropathy hereditary sensory radicular, autosomal dominant; Hereditary sensory neuropathy type 1; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018213; MedGen: C0020071; Orphanet: 36386

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001517688Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 14, 2022) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001517688.4

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

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. 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 SPTLC1 protein function. ClinVar contains an entry for this variant (Variation ID: 1026225). This variant has not been reported in the literature in individuals affected with SPTLC1-related conditions. This variant is present in population databases (rs769908505, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 240 of the SPTLC1 protein (p.Arg240Cys).

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

Last Updated: Feb 20, 2024