TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20428	61507;61508;61509	chr2:178590443;178590442;178590441	chr2:179455170;179455169;179455168
N2AB	18787	56584;56585;56586	chr2:178590443;178590442;178590441	chr2:179455170;179455169;179455168
N2A	17860	53803;53804;53805	chr2:178590443;178590442;178590441	chr2:179455170;179455169;179455168
N2B	11363	34312;34313;34314	chr2:178590443;178590442;178590441	chr2:179455170;179455169;179455168
Novex-1	11488	34687;34688;34689	chr2:178590443;178590442;178590441	chr2:179455170;179455169;179455168
Novex-2	11555	34888;34889;34890	chr2:178590443;178590442;178590441	chr2:179455170;179455169;179455168
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-36
• Domain position: 58
• Structural Position: 83
• Q(SASA): 0.7317
• 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
R/K	rs1158402913	0.068	0.001	N	0.177	0.092	0.0806252709748	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14758E-04	0	None	0	0	None	0	None	0	0	0
R/K	rs1158402913	0.068	0.001	N	0.177	0.092	0.0806252709748	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
R/K	rs1158402913	0.068	0.001	N	0.177	0.092	0.0806252709748	gnomAD-4.0.0	2.03012E-06	None	None	None	None	I	None	1.74752E-05	0	None	0	0	None	0	0	1.20498E-06	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
R/A	0.5325	ambiguous	0.486	ambiguous	0.126	Stabilizing	0.25	N	0.413	neutral	None	None	None	None	I
R/C	0.3032	likely_benign	0.3209	benign	-0.059	Destabilizing	0.992	D	0.391	neutral	None	None	None	None	I
R/D	0.7588	likely_pathogenic	0.746	pathogenic	-0.061	Destabilizing	0.617	D	0.475	neutral	None	None	None	None	I
R/E	0.4892	ambiguous	0.4667	ambiguous	0.015	Stabilizing	0.25	N	0.423	neutral	None	None	None	None	I
R/F	0.7442	likely_pathogenic	0.71	pathogenic	-0.015	Destabilizing	0.972	D	0.395	neutral	None	None	None	None	I
R/G	0.3684	ambiguous	0.3425	ambiguous	-0.084	Destabilizing	0.549	D	0.462	neutral	N	0.459515351	None	None	I
R/H	0.1572	likely_benign	0.157	benign	-0.592	Destabilizing	0.92	D	0.453	neutral	None	None	None	None	I
R/I	0.5147	ambiguous	0.4568	ambiguous	0.648	Stabilizing	0.92	D	0.421	neutral	None	None	None	None	I
R/K	0.1113	likely_benign	0.1148	benign	0.038	Stabilizing	0.001	N	0.177	neutral	N	0.373800521	None	None	I
R/L	0.3566	ambiguous	0.3328	benign	0.648	Stabilizing	0.617	D	0.462	neutral	None	None	None	None	I
R/M	0.4939	ambiguous	0.4516	ambiguous	0.093	Stabilizing	0.896	D	0.427	neutral	N	0.455145455	None	None	I
R/N	0.661	likely_pathogenic	0.6538	pathogenic	0.222	Stabilizing	0.617	D	0.409	neutral	None	None	None	None	I
R/P	0.347	ambiguous	0.326	benign	0.495	Stabilizing	0.92	D	0.425	neutral	None	None	None	None	I
R/Q	0.136	likely_benign	0.1325	benign	0.168	Stabilizing	0.021	N	0.253	neutral	None	None	None	None	I
R/S	0.5673	likely_pathogenic	0.5363	ambiguous	-0.067	Destabilizing	0.379	N	0.413	neutral	N	0.446103337	None	None	I
R/T	0.3508	ambiguous	0.3033	benign	0.146	Stabilizing	0.549	D	0.443	neutral	N	0.433270112	None	None	I
R/V	0.5358	ambiguous	0.4947	ambiguous	0.495	Stabilizing	0.617	D	0.424	neutral	None	None	None	None	I
R/W	0.3379	likely_benign	0.3106	benign	-0.086	Destabilizing	0.99	D	0.408	neutral	N	0.46675525	None	None	I
R/Y	0.5755	likely_pathogenic	0.5398	ambiguous	0.319	Stabilizing	0.92	D	0.421	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.