ClinVar Miner

Submissions for variant NM_001267550.2(TTN):c.38902C>T (p.Pro12968Ser) (rs192528655)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001086491 SCV000286626 likely benign Dilated cardiomyopathy 1G; Limb-girdle muscular dystrophy, type 2J 2020-11-12 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000239005 SCV000297082 uncertain significance not specified 2015-09-18 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000232547 SCV001152937 likely benign not provided 2018-08-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000232547 SCV001552826 likely benign not provided no assertion criteria provided clinical testing The TTN p.Pro12968Ser variant was not identified in the literature but was identified in dbSNP (ID: rs192528655) and ClinVar (classified as uncertain significance by Division of Genomic Diagnostics, Children's Hospital of Philadelphia, and likely benign by Invitae and CeGaT Praxis fuer Humangenetik Tuebingen). The variant was identified in control databases in 316 of 272918 chromosomes (2 homozygous) at a frequency of 0.001158 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Ashkenazi Jewish in 70 of 9814 chromosomes (freq: 0.007133), South Asian in 107 of 29718 chromosomes (freq: 0.003601), Other in 13 of 6870 chromosomes (freq: 0.001892), European (Finnish) in 27 of 24698 chromosomes (freq: 0.001093), European (non-Finnish) in 79 of 125250 chromosomes (freq: 0.000631), Latino in 19 of 34082 chromosomes (freq: 0.000558) and African in 1 of 23322 chromosomes (freq: 0.000043), but was not observed in the East Asian population. The p.Pro12968 residue has limited species conservation data and computational analyses (BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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