Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000036031 | SCV000059683 | uncertain significance | not specified | 2018-05-21 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Asp178Asn var iant in MYL3 has been reported in 3 individuals with hypertrophic cardiomyopathy (Weissler-Snir 2017, LMM Data), but has also been identified in 0.14% (44/30782 ) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http:// gnomad.broadinstitute.org/; dbSNP rs145520567). This variant is also reported in ClinVar (Variation ID 43128). Computational prediction tools and conservation a nalysis suggest that the p.Asp178Asn variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, wh ile the clinical significance of the p.Asp178Asn variant is uncertain, its frequ ency in the general population suggests that it is more likely to be benign. ACM G/AMP Criteria applied: PP3, PS4_Supporting, BS1. |
Gene |
RCV000587491 | SCV000208891 | uncertain significance | not provided | 2018-11-01 | criteria provided, single submitter | clinical testing | The D178N variant of uncertain significance in the MYL3 gene has been reported in one individual from a cohort with clinically confirmed HCM, though patient-specific details were not provided (Weissler-Snir et al., 2017). Bick et al. (2012) reported D178N as a variant of uncertain significance in two patients in the Framingham and Jackson Heart Study cohorts. The D178N variant has been identified in several probands referred to GeneDx for HCM genetic testing; segregation data are currently uninformative. This variant is observed in 56/276934 (0.02%) alleles from individuals of multiple ethnic backgrounds in large population cohorts (Lek et al., 2016). Nevertheless, the D178N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Finally, in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
Illumina Clinical Services Laboratory, |
RCV000262754 | SCV000444746 | uncertain significance | Hypertrophic cardiomyopathy | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000262754 | SCV000549162 | likely benign | Hypertrophic cardiomyopathy | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000587491 | SCV000696365 | likely benign | not provided | 2016-01-25 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV000769163 | SCV000900538 | uncertain significance | Cardiomyopathy | 2016-08-03 | criteria provided, single submitter | clinical testing | |
Color | RCV000769163 | SCV000904646 | likely benign | Cardiomyopathy | 2019-11-17 | criteria provided, single submitter | clinical testing |