NM_014585.5(SLC40A1):c.263G>C (p.Arg88Thr) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Nov 4, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000435183.1

Allele description

NM_014585.5(SLC40A1):c.263G>C (p.Arg88Thr)

Gene:
SLC40A1:solute carrier family 40 member 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q32.2
Genomic location:
Preferred name:
NM_014585.5(SLC40A1):c.263G>C (p.Arg88Thr)
HGVS:
  • NC_000002.12:g.189575169C>G
  • NG_009027.1:g.10643G>C
  • NM_014585.5:c.263G>C
  • NP_055400.1:p.Arg88Thr
  • LRG_837t1:c.263G>C
  • LRG_837:g.10643G>C
  • LRG_837p1:p.Arg88Thr
  • NC_000002.11:g.190439895C>G
Protein change:
R88T
Links:
dbSNP: rs1057521155
NCBI 1000 Genomes Browser:
rs1057521155
Molecular consequence:
  • NM_014585.5:c.263G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000521314GeneDxcriteria provided, single submitter
Likely pathogenic
(Nov 4, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000521314.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The R88T variant in the SLC40A1 gene has been reported previously in multiple individuals from a single family with iron overload (Bach et al., 2006). The R88T variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R88T variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A different variant at the same residue (R88G) has also been reported in multiple individuals with elevated ferritin (Callebaut et al., 2014; Detivaud et al., 2013; Cunat et al., 2007), supporting the functional importance of this residue. The R88T variant is a strong candidate for a pathogenic variant.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 21, 2018