TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1863	5812;5813;5814	chr2:178776277;178776276;178776275	chr2:179641004;179641003;179641002
N2AB	1863	5812;5813;5814	chr2:178776277;178776276;178776275	chr2:179641004;179641003;179641002
N2A	1863	5812;5813;5814	chr2:178776277;178776276;178776275	chr2:179641004;179641003;179641002
N2B	1817	5674;5675;5676	chr2:178776277;178776276;178776275	chr2:179641004;179641003;179641002
Novex-1	1817	5674;5675;5676	chr2:178776277;178776276;178776275	chr2:179641004;179641003;179641002
Novex-2	1817	5674;5675;5676	chr2:178776277;178776276;178776275	chr2:179641004;179641003;179641002
Novex-3	1863	5812;5813;5814	chr2:178776277;178776276;178776275	chr2:179641004;179641003;179641002

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-9
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.3611
• 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/K	None	None	0.997	N	0.475	0.325	0.348983352498	gnomAD-4.0.0	2.05225E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	1.7343E-04	1.7986E-06	0	0
R/S	rs763383772	-1.125	1.0	N	0.752	0.492	0.222439326576	gnomAD-2.1.1	3.98E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.8E-06	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	0.9738	likely_pathogenic	0.9815	pathogenic	-0.721	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	I
R/C	0.8882	likely_pathogenic	0.9085	pathogenic	-0.737	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
R/D	0.9947	likely_pathogenic	0.9954	pathogenic	0.046	Stabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
R/E	0.9518	likely_pathogenic	0.9613	pathogenic	0.197	Stabilizing	0.999	D	0.6	neutral	None	None	None	None	I
R/F	0.9833	likely_pathogenic	0.9858	pathogenic	-0.39	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
R/G	0.9732	likely_pathogenic	0.9786	pathogenic	-1.053	Destabilizing	1.0	D	0.725	prob.delet.	D	0.563356159	None	None	I
R/H	0.6727	likely_pathogenic	0.7075	pathogenic	-1.273	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
R/I	0.9313	likely_pathogenic	0.9372	pathogenic	0.18	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
R/K	0.5413	ambiguous	0.5784	pathogenic	-0.654	Destabilizing	0.997	D	0.475	neutral	N	0.4845441	None	None	I
R/L	0.8815	likely_pathogenic	0.8952	pathogenic	0.18	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
R/M	0.9551	likely_pathogenic	0.9608	pathogenic	-0.327	Destabilizing	1.0	D	0.759	deleterious	D	0.636336828	None	None	I
R/N	0.9901	likely_pathogenic	0.9921	pathogenic	-0.297	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
R/P	0.9952	likely_pathogenic	0.996	pathogenic	-0.1	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
R/Q	0.5892	likely_pathogenic	0.6467	pathogenic	-0.36	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
R/S	0.9826	likely_pathogenic	0.9866	pathogenic	-1.044	Destabilizing	1.0	D	0.752	deleterious	N	0.509482545	None	None	I
R/T	0.9635	likely_pathogenic	0.9717	pathogenic	-0.698	Destabilizing	1.0	D	0.741	deleterious	N	0.504018193	None	None	I
R/V	0.9393	likely_pathogenic	0.9466	pathogenic	-0.1	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	I
R/W	0.8795	likely_pathogenic	0.8901	pathogenic	-0.05	Destabilizing	1.0	D	0.747	deleterious	D	0.636996843	None	None	I
R/Y	0.9615	likely_pathogenic	0.9671	pathogenic	0.219	Stabilizing	1.0	D	0.771	deleterious	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.