NM_014053.4(FLVCR1):c.362A>G (p.Asn121Ser) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Aug 7, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001301479.1

Allele description [Variation Report for NM_014053.4(FLVCR1):c.362A>G (p.Asn121Ser)]

NM_014053.4(FLVCR1):c.362A>G (p.Asn121Ser)

Gene:
FLVCR1:FLVCR heme transporter 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q32.3
Genomic location:
Preferred name:
NM_014053.4(FLVCR1):c.362A>G (p.Asn121Ser)
HGVS:
  • NC_000001.11:g.212858814A>G
  • NG_028131.1:g.5560A>G
  • NM_014053.4:c.362A>GMANE SELECT
  • NP_054772.1:p.Asn121Ser
  • NC_000001.10:g.213032156A>G
Protein change:
N121S
Molecular consequence:
  • NM_014053.4:c.362A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001490650Invitaecriteria provided, single submitter
Uncertain significance
(Aug 7, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Clinically Focused Molecular Investigation of 1000 Consecutive Families with Inherited Retinal Disease.

Stone EM, Andorf JL, Whitmore SS, DeLuca AP, Giacalone JC, Streb LM, Braun TA, Mullins RF, Scheetz TE, Sheffield VC, Tucker BA.

Ophthalmology. 2017 Sep;124(9):1314-1331. doi: 10.1016/j.ophtha.2017.04.008. Epub 2017 May 27.

PubMed [citation]
PMID:
28559085
PMCID:
PMC5565704

Mutations in FLVCR1 cause posterior column ataxia and retinitis pigmentosa.

Rajadhyaksha AM, Elemento O, Puffenberger EG, Schierberl KC, Xiang JZ, Putorti ML, Berciano J, Poulin C, Brais B, Michaelides M, Weleber RG, Higgins JJ.

Am J Hum Genet. 2010 Nov 12;87(5):643-54. doi: 10.1016/j.ajhg.2010.10.013.

PubMed [citation]
PMID:
21070897
PMCID:
PMC2978959
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001490650.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces asparagine with serine at codon 121 of the FLVCR1 protein (p.Asn121Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FLVCR1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the p.Asn121 amino acid residue in FLVCR1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 28559085, 21070897). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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

Last Updated: Mar 12, 2021

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