TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16630	50113;50114;50115	chr2:178612833;178612832;178612831	chr2:179477560;179477559;179477558
N2AB	14989	45190;45191;45192	chr2:178612833;178612832;178612831	chr2:179477560;179477559;179477558
N2A	14062	42409;42410;42411	chr2:178612833;178612832;178612831	chr2:179477560;179477559;179477558
N2B	7565	22918;22919;22920	chr2:178612833;178612832;178612831	chr2:179477560;179477559;179477558
Novex-1	7690	23293;23294;23295	chr2:178612833;178612832;178612831	chr2:179477560;179477559;179477558
Novex-2	7757	23494;23495;23496	chr2:178612833;178612832;178612831	chr2:179477560;179477559;179477558
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: Fn3-8
• Domain position: 80
• Structural Position: 113
• Q(SASA): 0.7048
• 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	rs374031591	0.228	0.92	N	0.305	0.151	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	6.48E-05	0	None	0	0	None	0	None	0	0	0
K/E	rs374031591	0.228	0.92	N	0.305	0.151	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-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	0.2892	likely_benign	0.4274	ambiguous	0.076	Stabilizing	0.863	D	0.417	neutral	None	None	None	None	I
K/C	0.7749	likely_pathogenic	0.8269	pathogenic	-0.138	Destabilizing	0.999	D	0.433	neutral	None	None	None	None	I
K/D	0.6819	likely_pathogenic	0.8472	pathogenic	-0.116	Destabilizing	0.991	D	0.404	neutral	None	None	None	None	I
K/E	0.2268	likely_benign	0.4243	ambiguous	-0.126	Destabilizing	0.92	D	0.305	neutral	N	0.440501949	None	None	I
K/F	0.8167	likely_pathogenic	0.8963	pathogenic	-0.199	Destabilizing	0.991	D	0.473	neutral	None	None	None	None	I
K/G	0.513	ambiguous	0.6785	pathogenic	-0.094	Destabilizing	0.969	D	0.47	neutral	None	None	None	None	I
K/H	0.446	ambiguous	0.5263	ambiguous	-0.323	Destabilizing	0.997	D	0.39	neutral	None	None	None	None	I
K/I	0.2917	likely_benign	0.4099	ambiguous	0.441	Stabilizing	0.884	D	0.467	neutral	None	None	None	None	I
K/L	0.3446	ambiguous	0.4762	ambiguous	0.441	Stabilizing	0.759	D	0.465	neutral	None	None	None	None	I
K/M	0.2575	likely_benign	0.3738	ambiguous	0.228	Stabilizing	0.509	D	0.35	neutral	N	0.472576123	None	None	I
K/N	0.5278	ambiguous	0.7241	pathogenic	0.298	Stabilizing	0.988	D	0.309	neutral	N	0.480018277	None	None	I
K/P	0.6258	likely_pathogenic	0.7609	pathogenic	0.345	Stabilizing	0.997	D	0.419	neutral	None	None	None	None	I
K/Q	0.1751	likely_benign	0.2355	benign	0.101	Stabilizing	0.92	D	0.345	neutral	N	0.47597554	None	None	I
K/R	0.0957	likely_benign	0.0994	benign	0.047	Stabilizing	0.035	N	0.263	neutral	N	0.478036071	None	None	I
K/S	0.4492	ambiguous	0.6274	pathogenic	-0.126	Destabilizing	0.969	D	0.303	neutral	None	None	None	None	I
K/T	0.1906	likely_benign	0.3061	benign	-0.004	Destabilizing	0.92	D	0.428	neutral	N	0.480279361	None	None	I
K/V	0.2501	likely_benign	0.3418	ambiguous	0.345	Stabilizing	0.079	N	0.178	neutral	None	None	None	None	I
K/W	0.8578	likely_pathogenic	0.9092	pathogenic	-0.248	Destabilizing	0.999	D	0.503	neutral	None	None	None	None	I
K/Y	0.7553	likely_pathogenic	0.84	pathogenic	0.112	Stabilizing	0.997	D	0.479	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.