TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1301	4126;4127;4128	chr2:178779291;178779290;178779289	chr2:179644018;179644017;179644016
N2AB	1301	4126;4127;4128	chr2:178779291;178779290;178779289	chr2:179644018;179644017;179644016
N2A	1301	4126;4127;4128	chr2:178779291;178779290;178779289	chr2:179644018;179644017;179644016
N2B	1255	3988;3989;3990	chr2:178779291;178779290;178779289	chr2:179644018;179644017;179644016
Novex-1	1255	3988;3989;3990	chr2:178779291;178779290;178779289	chr2:179644018;179644017;179644016
Novex-2	1255	3988;3989;3990	chr2:178779291;178779290;178779289	chr2:179644018;179644017;179644016
Novex-3	1301	4126;4127;4128	chr2:178779291;178779290;178779289	chr2:179644018;179644017;179644016

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-5
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.8152
• Predicted PPI site: I

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/G	None	None	0.939	N	0.543	0.471	0.5452609689	gnomAD-4.0.0	1.59113E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85739E-06	0	0
R/K	None	None	0.76	N	0.583	0.247	0.260249123532	gnomAD-4.0.0	1.20069E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31292E-06	0	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	0.8988	likely_pathogenic	0.9031	pathogenic	-0.286	Destabilizing	0.953	D	0.593	neutral	None	None	None	None	I
R/C	0.586	likely_pathogenic	0.5399	ambiguous	-0.427	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	I
R/D	0.9712	likely_pathogenic	0.9752	pathogenic	0.007	Stabilizing	0.986	D	0.57	neutral	None	None	None	None	I
R/E	0.8326	likely_pathogenic	0.8469	pathogenic	0.113	Stabilizing	0.91	D	0.604	neutral	None	None	None	None	I
R/F	0.956	likely_pathogenic	0.9591	pathogenic	-0.32	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	I
R/G	0.8514	likely_pathogenic	0.8587	pathogenic	-0.537	Destabilizing	0.939	D	0.543	neutral	N	0.510785408	None	None	I
R/H	0.2518	likely_benign	0.2461	benign	-1.017	Destabilizing	0.993	D	0.647	neutral	None	None	None	None	I
R/I	0.8343	likely_pathogenic	0.825	pathogenic	0.36	Stabilizing	0.991	D	0.687	prob.neutral	N	0.48885559	None	None	I
R/K	0.2842	likely_benign	0.2704	benign	-0.282	Destabilizing	0.76	D	0.583	neutral	N	0.450311525	None	None	I
R/L	0.7517	likely_pathogenic	0.7498	pathogenic	0.36	Stabilizing	0.953	D	0.543	neutral	None	None	None	None	I
R/M	0.8587	likely_pathogenic	0.8587	pathogenic	-0.165	Destabilizing	0.999	D	0.604	neutral	None	None	None	None	I
R/N	0.9395	likely_pathogenic	0.9459	pathogenic	-0.068	Destabilizing	0.986	D	0.633	neutral	None	None	None	None	I
R/P	0.9711	likely_pathogenic	0.9812	pathogenic	0.166	Stabilizing	0.993	D	0.662	neutral	None	None	None	None	I
R/Q	0.2525	likely_benign	0.2483	benign	-0.128	Destabilizing	0.386	N	0.376	neutral	None	None	None	None	I
R/S	0.9035	likely_pathogenic	0.9046	pathogenic	-0.562	Destabilizing	0.939	D	0.603	neutral	N	0.459876114	None	None	I
R/T	0.7829	likely_pathogenic	0.7821	pathogenic	-0.29	Destabilizing	0.982	D	0.587	neutral	N	0.441061262	None	None	I
R/V	0.8389	likely_pathogenic	0.8302	pathogenic	0.166	Stabilizing	0.993	D	0.683	prob.neutral	None	None	None	None	I
R/W	0.6789	likely_pathogenic	0.6906	pathogenic	-0.242	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	I
R/Y	0.8729	likely_pathogenic	0.8823	pathogenic	0.122	Stabilizing	0.998	D	0.661	neutral	None	None	None	None	I

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.