TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13911	41956;41957;41958	chr2:178635593;178635592;178635591	chr2:179500320;179500319;179500318
N2AB	12270	37033;37034;37035	chr2:178635593;178635592;178635591	chr2:179500320;179500319;179500318
N2A	11343	34252;34253;34254	chr2:178635593;178635592;178635591	chr2:179500320;179500319;179500318
N2B	4846	14761;14762;14763	chr2:178635593;178635592;178635591	chr2:179500320;179500319;179500318
Novex-1	4971	15136;15137;15138	chr2:178635593;178635592;178635591	chr2:179500320;179500319;179500318
Novex-2	5038	15337;15338;15339	chr2:178635593;178635592;178635591	chr2:179500320;179500319;179500318
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-89
• Domain position: 36
• Structural Position: 55
• Q(SASA): 0.5187
• 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
D/N	rs1209898521	None	0.003	N	0.123	0.086	0.12205267543	gnomAD-4.0.0	6.93692E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.19523E-05	0
D/Y	rs1209898521	None	0.306	N	0.531	0.174	0.362361684037	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94024E-04	None	0	0	0	0	0
D/Y	rs1209898521	None	0.306	N	0.531	0.174	0.362361684037	gnomAD-4.0.0	6.57774E-06	None	None	None	None	N	None	0	0	None	0	1.94024E-04	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
D/A	0.3296	likely_benign	0.3538	ambiguous	-0.293	Destabilizing	0.094	N	0.325	neutral	N	0.438912266	None	None	N
D/C	0.877	likely_pathogenic	0.8786	pathogenic	-0.247	Destabilizing	0.964	D	0.401	neutral	None	None	None	None	N
D/E	0.1694	likely_benign	0.1735	benign	-0.287	Destabilizing	None	N	0.085	neutral	N	0.413521964	None	None	N
D/F	0.8663	likely_pathogenic	0.8862	pathogenic	0.052	Stabilizing	0.703	D	0.499	neutral	None	None	None	None	N
D/G	0.4519	ambiguous	0.4861	ambiguous	-0.52	Destabilizing	0.094	N	0.331	neutral	N	0.439832885	None	None	N
D/H	0.5903	likely_pathogenic	0.6027	pathogenic	0.4	Stabilizing	0.001	N	0.243	neutral	N	0.441955121	None	None	N
D/I	0.6478	likely_pathogenic	0.6586	pathogenic	0.27	Stabilizing	0.538	D	0.532	neutral	None	None	None	None	N
D/K	0.6646	likely_pathogenic	0.6396	pathogenic	0.281	Stabilizing	0.064	N	0.327	neutral	None	None	None	None	N
D/L	0.6739	likely_pathogenic	0.7025	pathogenic	0.27	Stabilizing	0.25	N	0.467	neutral	None	None	None	None	N
D/M	0.834	likely_pathogenic	0.8564	pathogenic	0.214	Stabilizing	0.878	D	0.4	neutral	None	None	None	None	N
D/N	0.2169	likely_benign	0.2174	benign	-0.309	Destabilizing	0.003	N	0.123	neutral	N	0.444448097	None	None	N
D/P	0.9753	likely_pathogenic	0.9797	pathogenic	0.105	Stabilizing	0.403	N	0.443	neutral	None	None	None	None	N
D/Q	0.5091	ambiguous	0.5159	ambiguous	-0.222	Destabilizing	0.143	N	0.187	neutral	None	None	None	None	N
D/R	0.6844	likely_pathogenic	0.688	pathogenic	0.6	Stabilizing	0.25	N	0.43	neutral	None	None	None	None	N
D/S	0.2455	likely_benign	0.2624	benign	-0.385	Destabilizing	0.064	N	0.242	neutral	None	None	None	None	N
D/T	0.3808	ambiguous	0.3831	ambiguous	-0.19	Destabilizing	0.004	N	0.229	neutral	None	None	None	None	N
D/V	0.4094	ambiguous	0.4285	ambiguous	0.105	Stabilizing	0.201	N	0.469	neutral	N	0.444659975	None	None	N
D/W	0.9676	likely_pathogenic	0.9709	pathogenic	0.257	Stabilizing	0.964	D	0.431	neutral	None	None	None	None	N
D/Y	0.5287	ambiguous	0.5573	ambiguous	0.308	Stabilizing	0.306	N	0.531	neutral	N	0.441955121	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.