ClinVar Miner

Submissions for variant NM_001159699.2(FHL1):c.816C>T (p.Ser272=)

gnomAD frequency: 0.00003  dbSNP: rs758552293
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001810666 SCV001477626 uncertain significance not provided 2021-04-27 criteria provided, single submitter clinical testing The FHL1 c.968C>T; p.Pro323Leu variant (rs758552293), also known as c.768C>T; p.Ser256Ser on the predominant transcript NM_001449.4, is not reported in the medical literature but is reported in the Leiden Open Variation Database. This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. The proline at codon 323 is weakly conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Although p.Pro323Leu occurs on only a small proportion (2-3%) of transcripts expressed in heart and skeletal muscle (GTEX database), another variant specific to these transcripts has been reported in two brothers with myopathy and cardiac involvement (Binder 2012 and Schoser 2009). Due to limited information, the clinical significance of the p.Pro323Leu variant is uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV001497641 SCV001702377 likely benign X-linked myopathy with postural muscle atrophy 2023-02-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV002402811 SCV002669504 likely benign Cardiovascular phenotype 2021-01-25 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.

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.