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.
ClinVar Genomic variation as it relates to human health
NM_001126105.2(SLC7A7):c.1005_1008del (p.Phe335Leufs)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(6)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic/Likely pathogenic
6
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001126105.2(SLC7A7):c.1005_1008del (p.Phe335Leufs)
Variation ID: 56346 Accession: VCV000056346.6
- Type and length
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Deletion, 4 bp
- Location
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Cytogenetic: 14q11.2 14: 22775531-22775534 (GRCh38) [ NCBI UCSC ] 14: 23244740-23244743 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jul 24, 2013 Oct 8, 2024 Nov 19, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_003982.4:c.1005_1008del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_003973.3:p.Phe335fs frameshift NM_001126105.2:c.1005_1008delCTTT NM_001126105.3:c.1005_1008del NP_001119577.1:p.Phe335fs frameshift NM_001126106.4:c.1005_1008del NP_001119578.1:p.Phe335fs frameshift NC_000014.9:g.22775534_22775537del NC_000014.8:g.23244743_23244746del NG_012851.2:g.59287_59290del LRG_695:g.59287_59290del LRG_695t2:c.1005_1008del LRG_695p2:p.Phe335fs LRG_695t3:c.1005_1008del LRG_695p3:p.Phe335fs - Protein change
- F335fs
- Other names
- -
- Canonical SPDI
- NC_000014.9:22775530:AAAGAAA:AAA
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| SLC7A7 | - | - |
GRCh38 GRCh37 |
756 | 821 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Nov 19, 2023 | RCV000049759.8 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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|---|---|---|---|---|---|
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Pathogenic
(Mar 14, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Lysinuric protein intolerance
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004202543.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
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Pathogenic
(Nov 19, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Lysinuric protein intolerance
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003442781.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 14, 2024 |
Comment:
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 … (more)
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. (less)
|
|
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Likely pathogenic
(Nov 05, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Lysinuric protein intolerance
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002776075.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
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Pathogenic
(May 20, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Lysinuric protein intolerance
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV005329632.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
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 … (more)
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. (less)
Clinical Features:
Abnormality of the immune system (present)
|
|
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probable-pathogenic
(-)
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no assertion criteria provided
Method: not provided
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Lysinuric protein intolerance
Affected status: not provided
Allele origin:
not provided
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Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)
Accession: SCV000082166.1
First in ClinVar: Jul 24, 2013 Last updated: Jul 24, 2013
Comment:
FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference
|
Comment:
Converted during submission to Likely pathogenic.
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Pathogenic
(Jan 01, 2008)
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no assertion criteria provided
Method: literature only
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LYSINURIC PROTEIN INTOLERANCE
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000026771.2
First in ClinVar: Apr 04, 2013 Last updated: Aug 20, 2015 |
Comment on evidence:
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 … (more)
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. (less)
|
Comment:
Comment:
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.
Comment:
Converted during submission to Likely pathogenic.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
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.
Comment:
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.
Comment:
Converted during submission to Likely pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Lysinuric protein intolerance: update and extended mutation analysis of the SLC7A7 gene. | Sperandeo MP | Human mutation | 2008 | PMID: 17764084 |
| Five novel SLC7A7 variants and y+L gene-expression pattern in cultured lymphoblasts from Japanese patients with lysinuric protein intolerance. | Shoji Y | Human mutation | 2002 | PMID: 12402335 |
| Functional analysis of novel mutations in y(+)LAT-1 amino acid transporter gene causing lysinuric protein intolerance (LPI). | Mykkänen J | Human molecular genetics | 2000 | PMID: 10655553 |
| Structure of the SLC7A7 gene and mutational analysis of patients affected by lysinuric protein intolerance. | Sperandeo MP | American journal of human genetics | 2000 | PMID: 10631139 |
| Identification of SLC7A7, encoding y+LAT-1, as the lysinuric protein intolerance gene. | Torrents D | Nature genetics | 1999 | PMID: 10080182 |
Text-mined citations for rs386833794 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.