NM_006415.4(SPTLC1):c.431T>A (p.Val144Asp) AND Hereditary sensory and autonomic neuropathy type 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 31, 2024
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:: RCV000005068.15

Allele description [Variation Report for NM_006415.4(SPTLC1):c.431T>A (p.Val144Asp)]

NM_006415.4(SPTLC1):c.431T>A (p.Val144Asp)

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.431T>A (p.Val144Asp)

HGVS:

NC_000009.12:g.92068095A>T
NG_007950.1:g.52314T>A
NM_001281303.2:c.431T>A
NM_001368272.1:c.65T>A
NM_001368273.1:c.-35T>A
NM_006415.4:c.431T>AMANE SELECT
NP_001268232.1:p.Val144Asp
NP_001355201.1:p.Val22Asp
NP_006406.1:p.Val144Asp
LRG_272t1:c.431T>A
LRG_272:g.52314T>A
LRG_272p1:p.Val144Asp
NC_000009.11:g.94830377A>T
NM_006415.2:c.431T>A
NM_006415.3:c.431T>A
O15269:p.Val144Asp

Protein change:

V144D; VAL144ASP

Links:

UniProtKB: O15269#VAR_011394; OMIM: 605712.0003; dbSNP: rs119482083

NCBI 1000 Genomes Browser:

rs119482083

Molecular consequence:

NM_001368273.1:c.-35T>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001281303.2:c.431T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001368272.1:c.65T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006415.4:c.431T>A - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000626933	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 31, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 11242114, 19132419, 24673574, 25584079, 26681808, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000626933

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 31, 2024)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

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

Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I.

Dawkins JL, Hulme DJ, Brahmbhatt SB, Auer-Grumbach M, Nicholson GA.

Nat Genet. 2001 Mar;27(3):309-12.

PubMed [citation]

PMID:: 11242114

A systematic comparison of all mutations in hereditary sensory neuropathy type I (HSAN I) reveals that the G387A mutation is not disease associated.

Hornemann T, Penno A, Richard S, Nicholson G, van Dijk FS, Rotthier A, Timmerman V, von Eckardstein A.

Neurogenetics. 2009 Apr;10(2):135-43. doi: 10.1007/s10048-008-0168-7. Epub 2009 Jan 9.

PubMed [citation]

PMID:: 19132419

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000626933.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 144 of the SPTLC1 protein (p.Val144Asp). This variant is present in population databases (rs119482083, gnomAD 0.002%). This missense change has been observed in individuals with hereditary sensory neuropathy (PMID: 11242114; Invitae). ClinVar contains an entry for this variant (Variation ID: 4801). 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 SPTLC1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects SPTLC1 function (PMID: 11242114, 19132419, 24673574, 25584079, 26681808). For these reasons, this variant has been classified as Pathogenic.

#	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: Oct 13, 2024

ClinVar

Relating variation to medicine