TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35439	106540;106541;106542	chr2:178530300;178530299;178530298	chr2:179395027;179395026;179395025
N2AB	33798	101617;101618;101619	chr2:178530300;178530299;178530298	chr2:179395027;179395026;179395025
N2A	32871	98836;98837;98838	chr2:178530300;178530299;178530298	chr2:179395027;179395026;179395025
N2B	26374	79345;79346;79347	chr2:178530300;178530299;178530298	chr2:179395027;179395026;179395025
Novex-1	26499	79720;79721;79722	chr2:178530300;178530299;178530298	chr2:179395027;179395026;179395025
Novex-2	26566	79921;79922;79923	chr2:178530300;178530299;178530298	chr2:179395027;179395026;179395025
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-166
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1446
• 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
F/L	None	None	None	N	0.226	0.214	0.0762999501168	gnomAD-4.0.0	1.36892E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79964E-06	0	0
F/S	None	None	0.49	D	0.698	0.648	0.791405280886	gnomAD-4.0.0	1.59251E-06	None	None	None	None	N	None	0	2.28697E-05	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
F/A	0.8866	likely_pathogenic	0.9228	pathogenic	-2.153	Highly Destabilizing	0.206	N	0.68	prob.neutral	None	None	None	None	N
F/C	0.8079	likely_pathogenic	0.8728	pathogenic	-1.796	Destabilizing	0.911	D	0.835	deleterious	D	0.580839812	None	None	N
F/D	0.99	likely_pathogenic	0.9929	pathogenic	-2.779	Highly Destabilizing	0.932	D	0.811	deleterious	None	None	None	None	N
F/E	0.9864	likely_pathogenic	0.9908	pathogenic	-2.563	Highly Destabilizing	0.817	D	0.787	deleterious	None	None	None	None	N
F/G	0.9628	likely_pathogenic	0.9745	pathogenic	-2.564	Highly Destabilizing	0.56	D	0.753	deleterious	None	None	None	None	N
F/H	0.958	likely_pathogenic	0.9684	pathogenic	-1.481	Destabilizing	0.932	D	0.753	deleterious	None	None	None	None	N
F/I	0.2678	likely_benign	0.3362	benign	-0.82	Destabilizing	0.089	N	0.473	neutral	N	0.510865836	None	None	N
F/K	0.9874	likely_pathogenic	0.9909	pathogenic	-2.205	Highly Destabilizing	0.56	D	0.77	deleterious	None	None	None	None	N
F/L	0.7818	likely_pathogenic	0.8253	pathogenic	-0.82	Destabilizing	None	N	0.226	neutral	N	0.386448184	None	None	N
F/M	0.5932	likely_pathogenic	0.6571	pathogenic	-0.766	Destabilizing	0.688	D	0.63	neutral	None	None	None	None	N
F/N	0.9698	likely_pathogenic	0.9782	pathogenic	-2.8	Highly Destabilizing	0.932	D	0.817	deleterious	None	None	None	None	N
F/P	0.9981	likely_pathogenic	0.9988	pathogenic	-1.274	Destabilizing	0.932	D	0.831	deleterious	None	None	None	None	N
F/Q	0.9806	likely_pathogenic	0.9868	pathogenic	-2.585	Highly Destabilizing	0.932	D	0.83	deleterious	None	None	None	None	N
F/R	0.975	likely_pathogenic	0.982	pathogenic	-2.063	Highly Destabilizing	0.817	D	0.8	deleterious	None	None	None	None	N
F/S	0.9398	likely_pathogenic	0.9603	pathogenic	-3.318	Highly Destabilizing	0.49	N	0.698	prob.neutral	D	0.580839812	None	None	N
F/T	0.908	likely_pathogenic	0.939	pathogenic	-2.98	Highly Destabilizing	0.386	N	0.707	prob.neutral	None	None	None	None	N
F/V	0.4036	ambiguous	0.4954	ambiguous	-1.274	Destabilizing	0.089	N	0.581	neutral	D	0.541188743	None	None	N
F/W	0.75	likely_pathogenic	0.7958	pathogenic	-0.239	Destabilizing	0.981	D	0.605	neutral	None	None	None	None	N
F/Y	0.3928	ambiguous	0.428	ambiguous	-0.572	Destabilizing	0.49	N	0.519	neutral	D	0.548599286	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.