TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28665	86218;86219;86220	chr2:178560139;178560138;178560137	chr2:179424866;179424865;179424864
N2AB	27024	81295;81296;81297	chr2:178560139;178560138;178560137	chr2:179424866;179424865;179424864
N2A	26097	78514;78515;78516	chr2:178560139;178560138;178560137	chr2:179424866;179424865;179424864
N2B	19600	59023;59024;59025	chr2:178560139;178560138;178560137	chr2:179424866;179424865;179424864
Novex-1	19725	59398;59399;59400	chr2:178560139;178560138;178560137	chr2:179424866;179424865;179424864
Novex-2	19792	59599;59600;59601	chr2:178560139;178560138;178560137	chr2:179424866;179424865;179424864
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-97
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.5883
• 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/E	rs1409897523	None	0.977	N	0.543	0.197	0.311079019809	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/E	rs1409897523	None	0.977	N	0.543	0.197	0.311079019809	gnomAD-4.0.0	6.5741E-06	None	None	None	None	N	None	2.41336E-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	0.516	ambiguous	0.4207	ambiguous	-0.087	Destabilizing	0.983	D	0.597	neutral	None	None	None	None	N
K/C	0.7989	likely_pathogenic	0.7174	pathogenic	-0.137	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
K/D	0.7143	likely_pathogenic	0.6483	pathogenic	None	Stabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
K/E	0.3088	likely_benign	0.2578	benign	-0.003	Destabilizing	0.977	D	0.543	neutral	N	0.446501273	None	None	N
K/F	0.8822	likely_pathogenic	0.8158	pathogenic	-0.395	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/G	0.5959	likely_pathogenic	0.4861	ambiguous	-0.29	Destabilizing	0.998	D	0.637	neutral	None	None	None	None	N
K/H	0.4291	ambiguous	0.3612	ambiguous	-0.728	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
K/I	0.5555	ambiguous	0.4698	ambiguous	0.369	Stabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
K/L	0.5044	ambiguous	0.4314	ambiguous	0.369	Stabilizing	0.995	D	0.637	neutral	None	None	None	None	N
K/M	0.3796	ambiguous	0.3089	benign	0.431	Stabilizing	1.0	D	0.677	prob.neutral	N	0.484143895	None	None	N
K/N	0.5748	likely_pathogenic	0.4907	ambiguous	0.258	Stabilizing	0.993	D	0.713	prob.delet.	N	0.490081479	None	None	N
K/P	0.6411	likely_pathogenic	0.5989	pathogenic	0.246	Stabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
K/Q	0.1921	likely_benign	0.1589	benign	-0.012	Destabilizing	0.993	D	0.71	prob.delet.	N	0.506397726	None	None	N
K/R	0.0866	likely_benign	0.0761	benign	0.015	Stabilizing	0.235	N	0.329	neutral	N	0.459259927	None	None	N
K/S	0.5738	likely_pathogenic	0.4718	ambiguous	-0.274	Destabilizing	0.983	D	0.639	neutral	None	None	None	None	N
K/T	0.3331	likely_benign	0.2745	benign	-0.128	Destabilizing	0.997	D	0.678	prob.neutral	N	0.501778553	None	None	N
K/V	0.5205	ambiguous	0.4439	ambiguous	0.246	Stabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
K/W	0.8771	likely_pathogenic	0.811	pathogenic	-0.357	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
K/Y	0.7529	likely_pathogenic	0.6722	pathogenic	0.019	Stabilizing	0.999	D	0.729	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.