NM_006996.3(SLC19A2):c.191T>C (p.Leu64Pro) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 2, 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:: RCV003084851.3

Allele description [Variation Report for NM_006996.3(SLC19A2):c.191T>C (p.Leu64Pro)]

NM_006996.3(SLC19A2):c.191T>C (p.Leu64Pro)

Gene:

SLC19A2:solute carrier family 19 member 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q24.2

Genomic location:

Preferred name:

NM_006996.3(SLC19A2):c.191T>C (p.Leu64Pro)

HGVS:

NC_000001.11:g.169485576A>G
NG_008255.1:g.5395T>C
NM_001319667.1:c.191T>C
NM_006996.3:c.191T>CMANE SELECT
NP_001306596.1:p.Leu64Pro
NP_008927.1:p.Leu64Pro
NC_000001.10:g.169454814A>G

Protein change:

L64P

Molecular consequence:

NM_001319667.1:c.191T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_006996.3:c.191T>C - 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
SCV003484009	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 2, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29450569, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003484009

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 2, 2022)

germline

clinical testing

PubMed (2)
[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

Pharmacogenomics in diabetes: outcomes of thiamine therapy in TRMA syndrome.

Habeb AM, Flanagan SE, Zulali MA, Abdullah MA, Pomahačová R, Boyadzhiev V, Colindres LE, Godoy GV, Vasanthi T, Al Saif R, Setoodeh A, Haghighi A, Haghighi A, Shaalan Y; International Neonatal Diabetes Consortium., Hattersley AT, Ellard S, De Franco E.

Diabetologia. 2018 May;61(5):1027-1036. doi: 10.1007/s00125-018-4554-x. Epub 2018 Feb 15.

PubMed [citation]

PMID:: 29450569
PMCID:: PMC6449001

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, SCV003484009.2

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 SLC19A2 protein function. This missense change has been observed in individual(s) with thiamine-responsive megaloblastic anemia syndrome (PMID: 29450569). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 64 of the SLC19A2 protein (p.Leu64Pro).

#	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: Sep 29, 2024

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