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NM_001371596.2(MFSD8):c.1235C>T (p.Pro412Leu) AND Inborn genetic diseases

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 11, 2016
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:
RCV002316184.9

Allele description [Variation Report for NM_001371596.2(MFSD8):c.1235C>T (p.Pro412Leu)]

NM_001371596.2(MFSD8):c.1235C>T (p.Pro412Leu)

Gene:
MFSD8:major facilitator superfamily domain containing 8 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q28.2
Genomic location:
Preferred name:
NM_001371596.2(MFSD8):c.1235C>T (p.Pro412Leu)
HGVS:
  • NC_000004.12:g.127921639G>A
  • NG_008657.1:g.49346C>T
  • NM_001363520.3:c.1034C>T
  • NM_001363521.3:c.920C>T
  • NM_001371590.2:c.1100C>T
  • NM_001371591.2:c.1235C>T
  • NM_001371592.2:c.1241C>T
  • NM_001371593.2:c.1121C>T
  • NM_001371594.2:c.1088C>T
  • NM_001371595.1:c.953C>T
  • NM_001371596.2:c.1235C>TMANE SELECT
  • NM_001410765.1:c.785C>T
  • NM_001410766.1:c.*120C>T
  • NM_152778.4:c.1235C>T
  • NP_001350449.1:p.Pro345Leu
  • NP_001350449.1:p.Pro345Leu
  • NP_001350450.1:p.Pro307Leu
  • NP_001350450.1:p.Pro307Leu
  • NP_001358519.1:p.Pro367Leu
  • NP_001358519.1:p.Pro367Leu
  • NP_001358520.1:p.Pro412Leu
  • NP_001358520.1:p.Pro412Leu
  • NP_001358521.1:p.Pro414Leu
  • NP_001358521.1:p.Pro414Leu
  • NP_001358522.1:p.Pro374Leu
  • NP_001358522.1:p.Pro374Leu
  • NP_001358523.1:p.Pro363Leu
  • NP_001358523.1:p.Pro363Leu
  • NP_001358524.1:p.Pro318Leu
  • NP_001358525.1:p.Pro412Leu
  • NP_001397694.1:p.Pro262Leu
  • NP_689991.1:p.Pro412Leu
  • LRG_833t1:c.1235C>T
  • LRG_833t2:c.1235C>T
  • LRG_833:g.49346C>T
  • LRG_833p1:p.Pro412Leu
  • LRG_833p2:p.Pro412Leu
  • NC_000004.11:g.128842794G>A
  • NM_001363520.2:c.1034C>T
  • NM_001363521.2:c.920C>T
  • NM_001371590.1:c.1100C>T
  • NM_001371591.1:c.1235C>T
  • NM_001371592.1:c.1241C>T
  • NM_001371593.1:c.1121C>T
  • NM_001371594.1:c.1088C>T
  • NM_152778.2:c.1235C>T
  • NM_152778.3:c.1235C>T
  • Q8NHS3:p.Pro412Leu
Protein change:
P262L; PRO412LEU
Links:
UniProtKB: Q8NHS3#VAR_072674; OMIM: 611124.0005; dbSNP: rs267607235
NCBI 1000 Genomes Browser:
rs267607235
Molecular consequence:
  • NM_001363520.3:c.1034C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363521.3:c.920C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371590.2:c.1100C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371591.2:c.1235C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371592.2:c.1241C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371593.2:c.1121C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371594.2:c.1088C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371595.1:c.953C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371596.2:c.1235C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001410765.1:c.785C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_152778.4:c.1235C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000850966Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Apr 11, 2016) 		germlineclinical testing

Citation Link

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Summary from all submissions

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

Details of each submission

From Ambry Genetics, SCV000850966.4

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

Description

The p.P412L variant (also known as c.1235C>T), located in coding exon 11 of the MFSD8 gene, results from a C to T substitution at nucleotide position 1235. The proline at codon 412 is replaced by leucine, an amino acid with similar properties. A study analyzing the functional proteolytic cleavage activity of this gene in COS-7 cells found that this variant resulted in increased proteolytic cleavage of the CLN7 protein in lysosomes presumably resulting in a non-functional protein (Steenhuis et al. Biochim Biophys Acta. 2012;1822 (10):1617-28). In another study, the p.P412L variant (referred to as c.1398C>T) was identified in a homozygous state in a consanguineous Saudi Arabian family with three affected children. The index case was a 10-year-old boy who developed progressive blindness, focal seizures with secondary generalized tonic clonic convulsions, and progressive decline in cognitive function in association with the Turkish variant of late-infantile Neuronal Ceroid Lipofuscinosis, characterized by a later age of onset and a more severe seizure phenotype (Aldahmesh et al. Neurogenetics. 2009;10:307-311). This variant was previously reported in the SNPDatabase as rs267607235. This variant was not reported in population-based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. In the ESP, this variant was not observed in 6,503 samples (13,006 alleles) with coverage at this position.This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Oct 13, 2024