TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9567	28924;28925;28926	chr2:178709620;178709619;178709618	chr2:179574347;179574346;179574345
N2AB	9250	27973;27974;27975	chr2:178709620;178709619;178709618	chr2:179574347;179574346;179574345
N2A	8323	25192;25193;25194	chr2:178709620;178709619;178709618	chr2:179574347;179574346;179574345
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-81
• Domain position: 75
• Structural Position: 157
• Q(SASA): 0.2558
• 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
K/N	rs2076366428	None	0.998	None	0.637	0.315	0.236890367714	gnomAD-4.0.0	3.42098E-06	None	None	None	None	N	None	1.49361E-04	0	None	0	0	None	0	0	0	0	0
K/T	rs770062038	-1.102	0.998	None	0.707	0.439	0.496957384516	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-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
K/A	0.7244	likely_pathogenic	0.7681	pathogenic	-0.988	Destabilizing	0.992	D	0.597	neutral	None	None	None	None	N
K/C	0.8826	likely_pathogenic	0.8913	pathogenic	-1.075	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
K/D	0.9388	likely_pathogenic	0.955	pathogenic	-0.307	Destabilizing	0.998	D	0.714	prob.delet.	None	None	None	None	N
K/E	0.4557	ambiguous	0.4965	ambiguous	-0.142	Destabilizing	0.978	D	0.519	neutral	None	None	None	None	N
K/F	0.9439	likely_pathogenic	0.952	pathogenic	-0.629	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
K/G	0.8889	likely_pathogenic	0.9053	pathogenic	-1.386	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
K/H	0.5399	ambiguous	0.5814	pathogenic	-1.623	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
K/I	0.6167	likely_pathogenic	0.6256	pathogenic	0.071	Stabilizing	0.999	D	0.787	deleterious	None	None	None	None	N
K/L	0.6362	likely_pathogenic	0.6631	pathogenic	0.071	Stabilizing	0.998	D	0.741	deleterious	None	None	None	None	N
K/M	0.4464	ambiguous	0.4695	ambiguous	-0.09	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
K/N	0.8167	likely_pathogenic	0.8557	pathogenic	-0.784	Destabilizing	0.998	D	0.637	neutral	None	None	None	None	N
K/P	0.994	likely_pathogenic	0.9962	pathogenic	-0.254	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/Q	0.2636	likely_benign	0.2781	benign	-0.795	Destabilizing	0.775	D	0.367	neutral	None	None	None	None	N
K/R	0.1027	likely_benign	0.1031	benign	-0.646	Destabilizing	0.989	D	0.491	neutral	None	None	None	None	N
K/S	0.7759	likely_pathogenic	0.8181	pathogenic	-1.556	Destabilizing	0.992	D	0.567	neutral	None	None	None	None	N
K/T	0.4419	ambiguous	0.4799	ambiguous	-1.158	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
K/V	0.5663	likely_pathogenic	0.5767	pathogenic	-0.254	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
K/W	0.9409	likely_pathogenic	0.9417	pathogenic	-0.454	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
K/Y	0.8674	likely_pathogenic	0.8881	pathogenic	-0.141	Destabilizing	1.0	D	0.782	deleterious	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.