TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2706	8341;8342;8343	chr2:178771211;178770675;178770674	chr2:179635938;179635402;179635401
N2AB	2706	8341;8342;8343	chr2:178771211;178770675;178770674	chr2:179635938;179635402;179635401
N2A	2706	8341;8342;8343	chr2:178771211;178770675;178770674	chr2:179635938;179635402;179635401
N2B	2660	8203;8204;8205	chr2:178771211;178770675;178770674	chr2:179635938;179635402;179635401
Novex-1	2660	8203;8204;8205	chr2:178771211;178770675;178770674	chr2:179635938;179635402;179635401
Novex-2	2660	8203;8204;8205	chr2:178771211;178770675;178770674	chr2:179635938;179635402;179635401
Novex-3	2706	8341;8342;8343	chr2:178771211;178770675;178770674	chr2:179635938;179635402;179635401

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-16
• Domain position: 86
• Structural Position: 178
• Q(SASA): 1.4119
• 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
A/D	None	None	0.993	D	0.66	None	0.771029458599	gnomAD-4.0.0	1.59984E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85696E-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
A/C	0.8548	likely_pathogenic	0.8798	pathogenic	-0.832	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
A/D	0.5244	ambiguous	0.5595	ambiguous	-0.681	Destabilizing	0.993	D	0.66	neutral	D	0.667140411	None	None	N
A/E	0.4922	ambiguous	0.4993	ambiguous	-0.822	Destabilizing	0.995	D	0.639	neutral	None	None	None	None	N
A/F	0.67	likely_pathogenic	0.6739	pathogenic	-0.847	Destabilizing	0.998	D	0.697	prob.neutral	None	None	None	None	N
A/G	0.2251	likely_benign	0.2328	benign	-0.29	Destabilizing	0.977	D	0.609	neutral	D	0.588207977	None	None	N
A/H	0.794	likely_pathogenic	0.7903	pathogenic	-0.26	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
A/I	0.5936	likely_pathogenic	0.5426	ambiguous	-0.327	Destabilizing	0.995	D	0.635	neutral	None	None	None	None	N
A/K	0.7546	likely_pathogenic	0.7402	pathogenic	-0.727	Destabilizing	0.995	D	0.64	neutral	None	None	None	None	N
A/L	0.4211	ambiguous	0.3815	ambiguous	-0.327	Destabilizing	0.966	D	0.584	neutral	None	None	None	None	N
A/M	0.4498	ambiguous	0.3801	ambiguous	-0.556	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
A/N	0.4831	ambiguous	0.4263	ambiguous	-0.399	Destabilizing	0.995	D	0.667	neutral	None	None	None	None	N
A/P	0.3673	ambiguous	0.3233	benign	-0.271	Destabilizing	0.997	D	0.63	neutral	D	0.676454309	None	None	N
A/Q	0.6287	likely_pathogenic	0.5786	pathogenic	-0.666	Destabilizing	0.998	D	0.652	neutral	None	None	None	None	N
A/R	0.6978	likely_pathogenic	0.6994	pathogenic	-0.248	Destabilizing	0.995	D	0.645	neutral	None	None	None	None	N
A/S	0.1573	likely_benign	0.1415	benign	-0.565	Destabilizing	0.955	D	0.575	neutral	D	0.629345651	None	None	N
A/T	0.2085	likely_benign	0.1529	benign	-0.632	Destabilizing	0.568	D	0.485	neutral	D	0.629345651	None	None	N
A/V	0.3084	likely_benign	0.2647	benign	-0.271	Destabilizing	0.955	D	0.609	neutral	D	0.667959533	None	None	N
A/W	0.9283	likely_pathogenic	0.9325	pathogenic	-0.984	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
A/Y	0.7684	likely_pathogenic	0.7863	pathogenic	-0.652	Destabilizing	1.0	D	0.694	prob.neutral	None	None	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.