NM_001003841.3(SLC6A19):c.697G>A (p.Val233Ile) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 24, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV002050745.6

Allele description [Variation Report for NM_001003841.3(SLC6A19):c.697G>A (p.Val233Ile)]

NM_001003841.3(SLC6A19):c.697G>A (p.Val233Ile)

Gene:

SLC6A19:solute carrier family 6 member 19 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5p15.33

Genomic location:

Preferred name:

NM_001003841.3(SLC6A19):c.697G>A (p.Val233Ile)

HGVS:

NC_000005.10:g.1213496G>A
NG_008282.1:g.16902G>A
NM_001003841.3:c.697G>AMANE SELECT
NP_001003841.1:p.Val233Ile
NC_000005.9:g.1213611G>A
NM_001003841.2:c.697G>A
NM_001003841.3:c.697G>A

Protein change:

V233I

Links:

dbSNP: rs183474162

NCBI 1000 Genomes Browser:

rs183474162

Molecular consequence:

NM_001003841.3:c.697G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002114796	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 24, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30626930, 28492532
SCV002758908	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jun 1, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002114796

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 24, 2024)

germline

clinical testing

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

SCV002758908

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Jun 1, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Value of genetic analysis for confirming inborn errors of metabolism detected through the Spanish neonatal screening program.

Navarrete R, Leal F, Vega AI, Morais-López A, Garcia-Silva MT, Martín-Hernández E, Quijada-Fraile P, Bergua A, Vives I, García-Jiménez I, Yahyaoui R, Pedrón-Giner C, Belanger-Quintana A, Stanescu S, Cañedo E, García-Campos O, Bueno-Delgado M, Delgado-Pecellín C, Vitoria I, Rausell MD, Balmaseda E, Couce ML, et al.

Eur J Hum Genet. 2019 Apr;27(4):556-562. doi: 10.1038/s41431-018-0330-0. Epub 2019 Jan 9.

PubMed [citation]

PMID:: 30626930
PMCID:: PMC6460639

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002114796.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 233 of the SLC6A19 protein (p.Val233Ile). This variant is present in population databases (rs183474162, gnomAD 0.02%). This missense change has been observed in individual(s) with a positive newborn screening result for SLC6A19-related disease (PMID: 30626930). ClinVar contains an entry for this variant (Variation ID: 1348032). 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 SLC6A19 protein function with a negative predictive value of 80%. 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.

#	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

From GeneDx, SCV002758908.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Identified via newborn screening study in a heterozygous individual who was classified as a carrier (Navarrete et al., 2019); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 30626930)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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