Submissions for variant NM_001267550.2(TTN):c.19801C>T (p.Pro6601Ser)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003331706	SCV004038836	uncertain significance	not specified	2023-08-22	criteria provided, single submitter	clinical testing	Variant summary: TTN c.16069C>T (p.Pro5357Ser) results in a non-conservative amino acid change located in the I-band region of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 248538 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.16069C>T has been reported in the literature in an individual(s) affected with Cardiomyopathy without cosegregation information and with other co-occurring variants (Mademont_Soler_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28771489, 30531895). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.