TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3289	10090;10091;10092	chr2:178764650;178764649;178764648	chr2:179629377;179629376;179629375
N2AB	3289	10090;10091;10092	chr2:178764650;178764649;178764648	chr2:179629377;179629376;179629375
N2A	3289	10090;10091;10092	chr2:178764650;178764649;178764648	chr2:179629377;179629376;179629375
N2B	3243	9952;9953;9954	chr2:178764650;178764649;178764648	chr2:179629377;179629376;179629375
Novex-1	3243	9952;9953;9954	chr2:178764650;178764649;178764648	chr2:179629377;179629376;179629375
Novex-2	3243	9952;9953;9954	chr2:178764650;178764649;178764648	chr2:179629377;179629376;179629375
Novex-3	3289	10090;10091;10092	chr2:178764650;178764649;178764648	chr2:179629377;179629376;179629375

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-23
• Domain position: 51
• Structural Position: 127
• Q(SASA): 0.6797
• 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
H/L	None	None	0.92	N	0.543	0.353	0.615448732319	gnomAD-4.0.0	6.8407E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99295E-07	0	0
H/R	rs758526828	-0.196	0.015	N	0.214	0.295	0.199424873507	gnomAD-2.1.1	7.97E-06	None	None	None	None	N	None	0	5.78E-05	None	0	0	None	0	None	0	0	0
H/R	rs758526828	-0.196	0.015	N	0.214	0.295	0.199424873507	gnomAD-4.0.0	5.47256E-06	None	None	None	None	N	None	0	1.3418E-04	None	0	0	None	0	0	8.99295E-07	1.15934E-05	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
H/A	0.5483	ambiguous	0.6585	pathogenic	0.338	Stabilizing	0.863	D	0.57	neutral	None	None	None	None	N
H/C	0.3672	ambiguous	0.5119	ambiguous	0.714	Stabilizing	0.1	N	0.495	neutral	None	None	None	None	N
H/D	0.5187	ambiguous	0.6759	pathogenic	0.057	Stabilizing	0.959	D	0.493	neutral	N	0.479305464	None	None	N
H/E	0.4425	ambiguous	0.5915	pathogenic	0.089	Stabilizing	0.884	D	0.394	neutral	None	None	None	None	N
H/F	0.5614	ambiguous	0.6451	pathogenic	1.042	Stabilizing	0.997	D	0.486	neutral	None	None	None	None	N
H/G	0.6	likely_pathogenic	0.722	pathogenic	0.056	Stabilizing	0.969	D	0.539	neutral	None	None	None	None	N
H/I	0.6474	likely_pathogenic	0.7393	pathogenic	1.058	Stabilizing	0.991	D	0.541	neutral	None	None	None	None	N
H/K	0.3564	ambiguous	0.484	ambiguous	0.345	Stabilizing	0.759	D	0.475	neutral	None	None	None	None	N
H/L	0.2699	likely_benign	0.3662	ambiguous	1.058	Stabilizing	0.92	D	0.543	neutral	N	0.50419406	None	None	N
H/M	0.7302	likely_pathogenic	0.7914	pathogenic	0.757	Stabilizing	0.997	D	0.523	neutral	None	None	None	None	N
H/N	0.2283	likely_benign	0.2932	benign	0.28	Stabilizing	0.959	D	0.419	neutral	N	0.48937075	None	None	N
H/P	0.5299	ambiguous	0.6926	pathogenic	0.843	Stabilizing	0.996	D	0.53	neutral	N	0.471231104	None	None	N
H/Q	0.2383	likely_benign	0.3216	benign	0.395	Stabilizing	0.31	N	0.258	neutral	N	0.483089017	None	None	N
H/R	0.1245	likely_benign	0.1869	benign	-0.25	Destabilizing	0.015	N	0.214	neutral	N	0.455966152	None	None	N
H/S	0.4102	ambiguous	0.4984	ambiguous	0.361	Stabilizing	0.939	D	0.481	neutral	None	None	None	None	N
H/T	0.519	ambiguous	0.6247	pathogenic	0.496	Stabilizing	0.969	D	0.553	neutral	None	None	None	None	N
H/V	0.533	ambiguous	0.6309	pathogenic	0.843	Stabilizing	0.939	D	0.535	neutral	None	None	None	None	N
H/W	0.5313	ambiguous	0.6268	pathogenic	1.039	Stabilizing	0.999	D	0.541	neutral	None	None	None	None	N
H/Y	0.174	likely_benign	0.2325	benign	1.302	Stabilizing	0.986	D	0.463	neutral	N	0.487886094	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.