Submissions for variant NM_000020.3(ACVRL1):c.74_77delinsGCTGCTGAGCTCAGGCGGTGCCAGGCCTGGGTCAGAATTGGAATTCTGCTGGGCAGGGAGTGGGCTGGAGACGGGCCAGGGCTAGGTTCTTCTTTCTGCAGGACCGGGGTGGAACGAGAGGCAGCTGGGGGTGGCCTGCCACTGGGTTTGGGTCTGGATTAAGTTAAACCTAAGG (p.Lys25_Pro26delinsSerCysTer)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002384885	SCV002671229	pathogenic	Cardiovascular phenotype	2020-09-11	criteria provided, single submitter	clinical testing	The c.74_77delAGCCins175 mutation, located in coding exon 2 of the ACVRL1 gene, results from the deletion of AGCC and insertion of 175 nucleotides causing a translational frameshift with a predicted alternate stop codon (p.K25Sfs*3). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003619779	SCV004473961	pathogenic	Telangiectasia, hereditary hemorrhagic, type 2	2024-01-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys25_Pro26delinsSerCys*) in the ACVRL1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACVRL1 are known to be pathogenic (PMID: 15879500). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ACVRL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1758744). For these reasons, this variant has been classified as Pathogenic.