TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15285	46078;46079;46080	chr2:178620757;178620756;178620755	chr2:179485484;179485483;179485482
N2AB	13644	41155;41156;41157	chr2:178620757;178620756;178620755	chr2:179485484;179485483;179485482
N2A	12717	38374;38375;38376	chr2:178620757;178620756;178620755	chr2:179485484;179485483;179485482
N2B	6220	18883;18884;18885	chr2:178620757;178620756;178620755	chr2:179485484;179485483;179485482
Novex-1	6345	19258;19259;19260	chr2:178620757;178620756;178620755	chr2:179485484;179485483;179485482
Novex-2	6412	19459;19460;19461	chr2:178620757;178620756;178620755	chr2:179485484;179485483;179485482
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-104
• Domain position: 78
• Structural Position: 163
• Q(SASA): 0.7775
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
R/S	rs794729439	None	1.0	N	0.635	0.34	0.256283259241	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.8226E-04	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
R/A	0.8291	likely_pathogenic	0.8394	pathogenic	0.093	Stabilizing	0.999	D	0.535	neutral	None	None	None	None	N
R/C	0.4103	ambiguous	0.46	ambiguous	0.183	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
R/D	0.9473	likely_pathogenic	0.949	pathogenic	-0.015	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
R/E	0.796	likely_pathogenic	0.8132	pathogenic	0.069	Stabilizing	0.999	D	0.586	neutral	None	None	None	None	N
R/F	0.8941	likely_pathogenic	0.9083	pathogenic	-0.013	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
R/G	0.7338	likely_pathogenic	0.7714	pathogenic	-0.144	Destabilizing	1.0	D	0.608	neutral	N	0.441104493	None	None	N
R/H	0.2287	likely_benign	0.2592	benign	-0.844	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
R/I	0.748	likely_pathogenic	0.7697	pathogenic	0.694	Stabilizing	1.0	D	0.742	deleterious	N	0.439756961	None	None	N
R/K	0.2983	likely_benign	0.2729	benign	0.124	Stabilizing	0.997	D	0.489	neutral	N	0.447346609	None	None	N
R/L	0.5707	likely_pathogenic	0.6064	pathogenic	0.694	Stabilizing	1.0	D	0.608	neutral	None	None	None	None	N
R/M	0.7565	likely_pathogenic	0.7703	pathogenic	0.23	Stabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
R/N	0.9121	likely_pathogenic	0.9122	pathogenic	0.465	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
R/P	0.9702	likely_pathogenic	0.9794	pathogenic	0.516	Stabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
R/Q	0.2208	likely_benign	0.2361	benign	0.378	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
R/S	0.8858	likely_pathogenic	0.9	pathogenic	0.136	Stabilizing	1.0	D	0.635	neutral	N	0.446946697	None	None	N
R/T	0.8206	likely_pathogenic	0.8357	pathogenic	0.367	Stabilizing	1.0	D	0.636	neutral	N	0.434046369	None	None	N
R/V	0.8305	likely_pathogenic	0.8452	pathogenic	0.516	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
R/W	0.4338	ambiguous	0.5022	ambiguous	-0.047	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
R/Y	0.7775	likely_pathogenic	0.7975	pathogenic	0.354	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.