NM_001126105.2(SLC7A7):c.1005_1008del (p.Phe335Leufs) AND Lysinuric protein intolerance

Germline classification:: Pathogenic/Likely pathogenic (6 submissions)
Last evaluated:: Nov 19, 2023
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:: RCV000049759.8

Allele description [Variation Report for NM_001126105.2(SLC7A7):c.1005_1008del (p.Phe335Leufs)]

NM_001126105.2(SLC7A7):c.1005_1008del (p.Phe335Leufs)

Gene:

SLC7A7:solute carrier family 7 member 7 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

14q11.2

Genomic location:

Preferred name:

NM_001126105.2(SLC7A7):c.1005_1008del (p.Phe335Leufs)

HGVS:

NC_000014.9:g.22775534_22775537del
NG_012851.2:g.59287_59290del
NM_001126105.3:c.1005_1008del
NM_001126106.4:c.1005_1008del
NM_003982.4:c.1005_1008delMANE SELECT
NP_001119577.1:p.Phe335fs
NP_001119578.1:p.Phe335fs
NP_001119578.1:p.Phe335fs
NP_003973.3:p.Phe335fs
LRG_695t2:c.1005_1008del
LRG_695t3:c.1005_1008del
LRG_695:g.59287_59290del
LRG_695p2:p.Phe335fs
LRG_695p3:p.Phe335fs
NC_000014.8:g.23244740_23244743del
NC_000014.8:g.23244743_23244746del
NM_001126105.2:c.1005_1008delCTTT
NM_001126106.2:c.1005_1008del
NM_003982.4:c.1005_1008del

Protein change:

F335fs

Links:

OMIM: 603593.0006; dbSNP: rs386833794

NCBI 1000 Genomes Browser:

rs386833794

Molecular consequence:

NM_001126105.3:c.1005_1008del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001126106.4:c.1005_1008del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003982.4:c.1005_1008del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Lysinuric protein intolerance (LPI)
Synonyms:: Dibasicamino aciduria II
Identifiers:: MONDO: MONDO:0009109; MedGen: C0268647; Orphanet: 470; OMIM: 222700

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000026771	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 2008)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 10080182, 17764084
SCV000082166	Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	no assertion criteria provided	probable-pathogenic	not provided	not provided	PubMed (3) [See all records that cite these PMIDs] 10080182, 10655553, 12402335
SCV002776075	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Nov 5, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003442781	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 19, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 10631139, 17764084, 10080182, 12402335, 28492532
SCV004202543	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 14, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005329632	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 20, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Description

FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference: SCV000082166

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Functional analysis of novel mutations in y(+)LAT-1 amino acid transporter gene causing lysinuric protein intolerance (LPI).

Mykkänen J, Torrents D, Pineda M, Camps M, Yoldi ME, Horelli-Kuitunen N, Huoponen K, Heinonen M, Oksanen J, Simell O, Savontaus ML, Zorzano A, Palacín M, Aula P.

Hum Mol Genet. 2000 Feb 12;9(3):431-8.

PubMed [citation]

PMID:: 10655553

Structure of the SLC7A7 gene and mutational analysis of patients affected by lysinuric protein intolerance.

Sperandeo MP, Bassi MT, Riboni M, Parenti G, Buoninconti A, Manzoni M, Incerti B, Larocca MR, Di Rocco M, Strisciuglio P, Dianzani I, Parini R, Candito M, Endo F, Ballabio A, Andria G, Sebastio G, Borsani G.

Am J Hum Genet. 2000 Jan;66(1):92-9.

PubMed [citation]

PMID:: 10631139
PMCID:: PMC1288352

See all PubMed Citations (7)

Details of each submission

From OMIM, SCV000026771.2

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

Description

For discussion of the 4-bp deletion (1005delCTTT) in the SLC7A7 gene that was found in compound heterozygous state in a patient with lysinuric protein intolerance (LPI; 222700) by Torrents et al. (1999), see 603593.0005. The authors originally cited this mutation as 1291delCTTT.

Sperandeo et al. (2008) noted that this mutation corresponds to 1005delCTTT in exon 8 of the SLC7A7 gene in the current nomenclature system.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM), SCV000082166.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	not provided	PubMed (3)

Description

Converted during submission to Likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not provided	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV002776075.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003442781.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Phe335Leufs*15) in the SLC7A7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SLC7A7 are known to be pathogenic (PMID: 10631139, 17764084). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with lysinuric protein intolerance (PMID: 10080182, 12402335). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as 1291delCTTT. ClinVar contains an entry for this variant (Variation ID: 56346). 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 Baylor Genetics, SCV004202543.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV005329632.1

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

Description

The observed frameshift variant c.1005_1008del(p.Phe335LeufsTer15) in SLC7A7 gene has been reported previously in homozygous and compound heterozygous state in individuals with lysinuric protein intolerance (Sperandeo MP, et al., 2008, Shoji Y, et al., 2002). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) with a pathogenic variant (Torrents D, et al., 1999). The c.1005_1008del variant is absent in gnomAD Exomes. This variant has been submitted to the ClinVar database as Pathogenic/Likely Pathogenic.This variant causes a frameshift starting with codon Phenylalanine 335, changes this amino acid to Leucine residue, and creates a premature Stop codon at position 15 of the new reading frame, denoted p.Phe335LeufsTer15. The variant is predicted to be likely damaging by SpliceAI Prediction. For these reasons, this variant has been classified as Pathogenic. In the absence of another reportable variant, the molecular diagnosis is not confirmed.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

Relating variation to medicine