Submissions for variant NM_002294.3(LAMP2):c.517G>A (p.Val173Ile)

gnomAD frequency: 0.00004  dbSNP: rs141574558

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037420	SCV000061077	uncertain significance	not specified	2014-02-28	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Val173Ile varia nt in LAMP2 has been previously reported by our laboratory in 2 individuals with HCM who were also carriers of a pathogenic variant in another HCM gene. It has also been identified in 2/6728 European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu; dbSNP rs141574558). Computati onal prediction tools suggest that this variant may not impact the protein, thou gh this information is not predictive enough to rule out pathogenicity. Valine ( Val) at position 173 is not conserved in mammals or evolutionarily distant speci es, with one mammal (Chinese tree shrew) and some fish having this variant (Ile) at this position, further supporting that a change at this position may be tole rated. Furthermore, nearly all disease-causing variants in LAMP2 have been trunc ating, while this is a missense variant. In summary, although this data supports that the Val173Ile variant may be more likely benign, additional studies are ne eded to fully assess its clinical significance.
GeneDx	RCV001697132	SCV000532767	likely benign	not provided	2019-11-15	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27532257)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000638586	SCV000760118	likely benign	Danon disease	2024-01-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002336130	SCV002644140	likely benign	Cardiovascular phenotype	2019-11-08	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV001697132	SCV004701180	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	LAMP2: BP4, BS2