ClinVar Miner

Submissions for variant NM_000258.3(MYL3):c.532G>A (p.Asp178Asn) (rs145520567)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized 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.
GeneDx 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,Illumina RCV000262754 SCV000444746 uncertain significance Hypertrophic cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000262754 SCV000549162 likely benign Hypertrophic cardiomyopathy 2020-12-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587491 SCV000696365 likely benign not provided 2016-01-25 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769163 SCV000900538 uncertain significance Cardiomyopathy 2016-08-03 criteria provided, single submitter clinical testing
Color Health, Inc RCV000769163 SCV000904646 likely benign Cardiomyopathy 2019-11-17 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.