NM_006996.3(SLC19A2):c.196G>T (p.Glu66Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jul 31, 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:: RCV002648219.4

Allele description [Variation Report for NM_006996.3(SLC19A2):c.196G>T (p.Glu66Ter)]

NM_006996.3(SLC19A2):c.196G>T (p.Glu66Ter)

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.196G>T (p.Glu66Ter)

HGVS:

NC_000001.11:g.169485571C>A
NG_008255.1:g.5400G>T
NM_001319667.1:c.196G>T
NM_006996.3:c.196G>TMANE SELECT
NP_001306596.1:p.Glu66Ter
NP_008927.1:p.Glu66Ter
NC_000001.10:g.169454809C>A

Protein change:

E66*

Molecular consequence:

NM_001319667.1:c.196G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_006996.3:c.196G>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV003523978	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 23, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 10391221, 10391223, 10874303, 28492532
SCV005090875	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 31, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003523978

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 23, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV005090875

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 31, 2024)

germline

clinical testing

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

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 SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness.

Labay V, Raz T, Baron D, Mandel H, Williams H, Barrett T, Szargel R, McDonald L, Shalata A, Nosaka K, Gregory S, Cohen N.

Nat Genet. 1999 Jul;22(3):300-4.

PubMed [citation]

PMID:: 10391221

Mutations in a new gene encoding a thiamine transporter cause thiamine-responsive megaloblastic anaemia syndrome.

Diaz GA, Banikazemi M, Oishi K, Desnick RJ, Gelb BD.

Nat Genet. 1999 Jul;22(3):309-12.

PubMed [citation]

PMID:: 10391223

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003523978.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Glu66*) in the SLC19A2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC19A2 are known to be pathogenic (PMID: 10391221, 10391223, 10874303). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with thiamine responsive megaloblastic anemia (PMID: 10874303). It has also been observed to segregate with disease in related individuals. This variant is also known as E65X. 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

From Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, SCV005090875.1

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

#	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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