TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4872	14839;14840;14841	chr2:178735832;178735831;178735830	chr2:179600559;179600558;179600557
N2AB	4555	13888;13889;13890	chr2:178735832;178735831;178735830	chr2:179600559;179600558;179600557
N2A	3628	11107;11108;11109	chr2:178735832;178735831;178735830	chr2:179600559;179600558;179600557
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: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-31
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.792
• 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
K/E	None	None	0.134	N	0.324	0.141	0.249502417897	gnomAD-4.0.0	1.59145E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43279E-05	0
K/N	rs771719584	0.229	0.92	N	0.431	0.258	0.173771789658	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
K/N	rs771719584	0.229	0.92	N	0.431	0.258	0.173771789658	gnomAD-4.0.0	4.10548E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49735E-06	0	1.657E-05

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	0.4911	ambiguous	0.4903	ambiguous	-0.115	Destabilizing	0.759	D	0.421	neutral	None	None	None	None	I
K/C	0.86	likely_pathogenic	0.8407	pathogenic	-0.499	Destabilizing	0.999	D	0.469	neutral	None	None	None	None	I
K/D	0.702	likely_pathogenic	0.7521	pathogenic	-0.115	Destabilizing	0.884	D	0.453	neutral	None	None	None	None	I
K/E	0.3123	likely_benign	0.3249	benign	-0.105	Destabilizing	0.134	N	0.324	neutral	N	0.407515966	None	None	I
K/F	0.9023	likely_pathogenic	0.9113	pathogenic	-0.424	Destabilizing	0.997	D	0.454	neutral	None	None	None	None	I
K/G	0.6899	likely_pathogenic	0.7078	pathogenic	-0.271	Destabilizing	0.939	D	0.453	neutral	None	None	None	None	I
K/H	0.4646	ambiguous	0.4636	ambiguous	-0.416	Destabilizing	0.997	D	0.457	neutral	None	None	None	None	I
K/I	0.4476	ambiguous	0.4397	ambiguous	0.217	Stabilizing	0.991	D	0.467	neutral	None	None	None	None	I
K/L	0.5106	ambiguous	0.5087	ambiguous	0.217	Stabilizing	0.969	D	0.486	neutral	None	None	None	None	I
K/M	0.3847	ambiguous	0.3706	ambiguous	-0.147	Destabilizing	0.999	D	0.455	neutral	N	0.503377941	None	None	I
K/N	0.5685	likely_pathogenic	0.6072	pathogenic	-0.073	Destabilizing	0.92	D	0.431	neutral	N	0.480226906	None	None	I
K/P	0.7107	likely_pathogenic	0.6745	pathogenic	0.132	Stabilizing	0.991	D	0.435	neutral	None	None	None	None	I
K/Q	0.2186	likely_benign	0.2181	benign	-0.168	Destabilizing	0.92	D	0.447	neutral	N	0.479088522	None	None	I
K/R	0.0988	likely_benign	0.0958	benign	-0.12	Destabilizing	0.92	D	0.454	neutral	N	0.402287824	None	None	I
K/S	0.5552	ambiguous	0.5913	pathogenic	-0.48	Destabilizing	0.2	N	0.254	neutral	None	None	None	None	I
K/T	0.2576	likely_benign	0.2595	benign	-0.331	Destabilizing	0.852	D	0.473	neutral	N	0.460788486	None	None	I
K/V	0.4416	ambiguous	0.4382	ambiguous	0.132	Stabilizing	0.969	D	0.455	neutral	None	None	None	None	I
K/W	0.9032	likely_pathogenic	0.9079	pathogenic	-0.508	Destabilizing	0.999	D	0.535	neutral	None	None	None	None	I
K/Y	0.7638	likely_pathogenic	0.7629	pathogenic	-0.151	Destabilizing	0.997	D	0.472	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.