TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21788	65587;65588;65589	chr2:178583820;178583819;178583818	chr2:179448547;179448546;179448545
N2AB	20147	60664;60665;60666	chr2:178583820;178583819;178583818	chr2:179448547;179448546;179448545
N2A	19220	57883;57884;57885	chr2:178583820;178583819;178583818	chr2:179448547;179448546;179448545
N2B	12723	38392;38393;38394	chr2:178583820;178583819;178583818	chr2:179448547;179448546;179448545
Novex-1	12848	38767;38768;38769	chr2:178583820;178583819;178583818	chr2:179448547;179448546;179448545
Novex-2	12915	38968;38969;38970	chr2:178583820;178583819;178583818	chr2:179448547;179448546;179448545
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: Fn3-46
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.5811
• 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/I	None	None	0.781	N	0.697	0.318	0.512825096792	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	7.32654E-05
K/N	None	None	0.638	N	0.662	0.227	0.186928172975	gnomAD-4.0.0	3.20148E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.74363E-06	0	0
K/T	rs1330714909	None	0.638	N	0.631	0.22	0.28297238246	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
K/T	rs1330714909	None	0.638	N	0.631	0.22	0.28297238246	gnomAD-4.0.0	1.31546E-05	None	None	None	None	N	None	4.82975E-05	0	None	0	0	None	0	0	0	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
K/A	0.5807	likely_pathogenic	0.4777	ambiguous	0.045	Stabilizing	0.399	N	0.605	neutral	None	None	None	None	N
K/C	0.8497	likely_pathogenic	0.7663	pathogenic	-0.292	Destabilizing	0.982	D	0.709	prob.delet.	None	None	None	None	N
K/D	0.8278	likely_pathogenic	0.7494	pathogenic	None	Stabilizing	0.7	D	0.672	neutral	None	None	None	None	N
K/E	0.4211	ambiguous	0.3427	ambiguous	-0.002	Destabilizing	0.201	N	0.57	neutral	N	0.488155895	None	None	N
K/F	0.9382	likely_pathogenic	0.8944	pathogenic	-0.229	Destabilizing	0.947	D	0.676	prob.neutral	None	None	None	None	N
K/G	0.7235	likely_pathogenic	0.6088	pathogenic	-0.121	Destabilizing	0.7	D	0.585	neutral	None	None	None	None	N
K/H	0.5005	ambiguous	0.3919	ambiguous	-0.29	Destabilizing	0.947	D	0.649	neutral	None	None	None	None	N
K/I	0.6571	likely_pathogenic	0.5711	pathogenic	0.398	Stabilizing	0.781	D	0.697	prob.neutral	N	0.483005033	None	None	N
K/L	0.6258	likely_pathogenic	0.5331	ambiguous	0.398	Stabilizing	0.7	D	0.585	neutral	None	None	None	None	N
K/M	0.5017	ambiguous	0.4343	ambiguous	0.115	Stabilizing	0.982	D	0.644	neutral	None	None	None	None	N
K/N	0.7028	likely_pathogenic	0.6008	pathogenic	0.18	Stabilizing	0.638	D	0.662	neutral	N	0.473027853	None	None	N
K/P	0.6579	likely_pathogenic	0.566	pathogenic	0.307	Stabilizing	0.826	D	0.668	neutral	None	None	None	None	N
K/Q	0.2352	likely_benign	0.1844	benign	0.022	Stabilizing	0.638	D	0.677	prob.neutral	N	0.521385821	None	None	N
K/R	0.0852	likely_benign	0.0734	benign	0.005	Stabilizing	0.002	N	0.208	neutral	N	0.466052613	None	None	N
K/S	0.6929	likely_pathogenic	0.5963	pathogenic	-0.27	Destabilizing	0.399	N	0.61	neutral	None	None	None	None	N
K/T	0.4245	ambiguous	0.3509	ambiguous	-0.135	Destabilizing	0.638	D	0.631	neutral	N	0.502626702	None	None	N
K/V	0.5501	ambiguous	0.4736	ambiguous	0.307	Stabilizing	0.7	D	0.675	prob.neutral	None	None	None	None	N
K/W	0.9168	likely_pathogenic	0.8556	pathogenic	-0.284	Destabilizing	0.982	D	0.733	prob.delet.	None	None	None	None	N
K/Y	0.859	likely_pathogenic	0.7819	pathogenic	0.079	Stabilizing	0.826	D	0.683	prob.neutral	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.