Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular 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. |
| Gene |
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) |
| Invitae | 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. |
| Ce |
RCV001697132 | SCV004701180 | likely benign | not provided | 2024-01-01 | criteria provided, single submitter | clinical testing | LAMP2: BP4, BS2 |