Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_006767.4(LZTR1):c.1084C>T (p.Arg362Ter)

CA10118715

289969 (ClinVar)

Gene: LZTR1
Condition: RASopathy
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 0dae1a0a-5bd8-4c2c-b2d0-d06f2eb3f8bd
Approved on: 2024-09-17
Published on: 2024-09-30

HGVS expressions

NM_006767.4:c.1084C>T
NM_006767.4(LZTR1):c.1084C>T (p.Arg362Ter)
NC_000022.11:g.20992304C>T
CM000684.2:g.20992304C>T
NC_000022.10:g.21346593C>T
CM000684.1:g.21346593C>T
NC_000022.9:g.19676593C>T
NG_034193.1:g.15036C>T
ENST00000700578.1:c.1084C>T
ENST00000495142.6:n.429C>T
ENST00000642151.1:c.915C>T
ENST00000643578.1:n.1106C>T
ENST00000646124.2:c.1084C>T
ENST00000646506.1:n.663C>T
ENST00000215739.12:c.1084C>T
ENST00000461510.1:n.185C>T
ENST00000479606.5:n.1230C>T
ENST00000492480.1:n.140C>T
ENST00000497716.5:n.911C>T
NM_006767.3:c.1084C>T
More

Likely Pathogenic

Met criteria codes 2
PVS1 PM3
Not Met criteria codes 3
BA1 PM2 BS1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for LZTR1 Version 1.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
RASopathy VCEP
The NM_006767.4:c.1084C>T (p.Arg362Ter) variant in LZTR1 is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 10/21 and lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). The highest population filtering allele frequency in gnomAD v2.1 is 0.00003426 (15/251042 alleles) in the European (non-Finnish) population. Evidence supports that this variant is associated with AR NS and is not associated with AD NS. This variant has been detected in 1 individual with NS. That individual was compound heterozygous for the variant and another loss of function pathogenic variant confirmed in trans by parental testing (c.1149+1G>T) (PM3, PMID:31182298). Schwannomatosis has been observed in individuals harboring this variant (PMID:29384852). In summary, this variant meets the criteria to be classified as pathogenic for autosomal recessive RASopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy VCEP: PM3, PVS1. (RASopathy VCEP specifications version 1.1; 9/17/2024).
Met criteria codes
PVS1
The NM_006767.4:c.1084C>T (p.Arg362Ter) variant in LZTR1 is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 10/21 and lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).
PM3
This variant has been detected in 1 individual with NS. That individual was compound heterozygous for the variant and another loss of function pathogenic variant confirmed in trans by parental testing (c.1149+1G>T) (PM3, PMID:31182298).
Not Met criteria codes
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
The highest population filtering allele frequency in gnomAD v2.1 is 0.00003426 (15/251042 alleles) in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met). This variant is present in gnomAD v2.1 at a frequency of 0.00003426 (15/251042)
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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