NM_006415.4(SPTLC1):c.431T>A (p.Val144Asp) AND Inborn genetic diseases

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 19, 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:: RCV002326664.2

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

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:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002632102	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Jan 19, 2022)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 11242114, 19132419, 24673574, 25584079, 26681808, 30420926, 32399692, 8673084 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002632102

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Jan 19, 2022)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

Citation Link

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 (8)

Details of each submission

From Ambry Genetics, SCV002632102.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

The p.V144D variant (also known as c.431T>A), located in coding exon 6 of the SPTLC1 gene, results from a T to A substitution at nucleotide position 431. The valine at codon 144 is replaced by aspartic acid, an amino acid with highly dissimilar properties. The p.V144D alteration has been reported to co-segregate with disease in several families with sensory neuropathy (Nicholson GA et al. Nat. Genet., 1996 May;13:101-4; Dawkins JL et al. Nat. Genet., 2001 Mar;27:309-12; Ho KWD et al. Case Rep Genet, 2018 Oct;2018:1898151; Vogt B et al. J Neurol, 2020 Sep;267:2648-2654). The functional studies of V144D show an impact on mitochondrial structure and protein expression; however, a direct link to the mechanism of pathology is not clear and enzymatic activity studies are conflicting (Hornemann T et al. Neurogenetics, 2009 Apr;10:135-43; Myers SJ et al. DNA Cell Biol., 2014 Jul;33:399-407; Stimpson SE et al. J Chem Biol, 2015 Jan;8:25-35; Bode H et al. Hum. Mol. Genet., 2016 Mar;25:853-65). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be 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: Apr 12, 2026

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