TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25020	75283;75284;75285	chr2:178571074;178571073;178571072	chr2:179435801;179435800;179435799
N2AB	23379	70360;70361;70362	chr2:178571074;178571073;178571072	chr2:179435801;179435800;179435799
N2A	22452	67579;67580;67581	chr2:178571074;178571073;178571072	chr2:179435801;179435800;179435799
N2B	15955	48088;48089;48090	chr2:178571074;178571073;178571072	chr2:179435801;179435800;179435799
Novex-1	16080	48463;48464;48465	chr2:178571074;178571073;178571072	chr2:179435801;179435800;179435799
Novex-2	16147	48664;48665;48666	chr2:178571074;178571073;178571072	chr2:179435801;179435800;179435799
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: Fn3-70
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.3978
• 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
R/K	None	None	0.025	N	0.216	0.097	0.225215365344	gnomAD-4.0.0	1.59324E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.8848E-05	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
R/A	0.8904	likely_pathogenic	0.8526	pathogenic	-0.468	Destabilizing	0.845	D	0.645	neutral	None	None	None	None	N
R/C	0.587	likely_pathogenic	0.5195	ambiguous	-0.344	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
R/D	0.9778	likely_pathogenic	0.9675	pathogenic	-0.249	Destabilizing	0.975	D	0.681	prob.neutral	None	None	None	None	N
R/E	0.8681	likely_pathogenic	0.8287	pathogenic	-0.187	Destabilizing	0.845	D	0.567	neutral	None	None	None	None	N
R/F	0.9826	likely_pathogenic	0.9737	pathogenic	-0.689	Destabilizing	0.996	D	0.755	deleterious	None	None	None	None	N
R/G	0.7408	likely_pathogenic	0.6529	pathogenic	-0.697	Destabilizing	0.892	D	0.615	neutral	N	0.476458821	None	None	N
R/H	0.4213	ambiguous	0.3585	ambiguous	-1.125	Destabilizing	0.987	D	0.583	neutral	None	None	None	None	N
R/I	0.9411	likely_pathogenic	0.9179	pathogenic	0.116	Stabilizing	0.987	D	0.756	deleterious	None	None	None	None	N
R/K	0.2243	likely_benign	0.2049	benign	-0.517	Destabilizing	0.025	N	0.216	neutral	N	0.401654418	None	None	N
R/L	0.8744	likely_pathogenic	0.8389	pathogenic	0.116	Stabilizing	0.916	D	0.615	neutral	None	None	None	None	N
R/M	0.9074	likely_pathogenic	0.8708	pathogenic	0.005	Stabilizing	0.999	D	0.609	neutral	N	0.494904316	None	None	N
R/N	0.9479	likely_pathogenic	0.9275	pathogenic	0.023	Stabilizing	0.975	D	0.591	neutral	None	None	None	None	N
R/P	0.9375	likely_pathogenic	0.9191	pathogenic	-0.059	Destabilizing	0.987	D	0.711	prob.delet.	None	None	None	None	N
R/Q	0.3325	likely_benign	0.2837	benign	-0.251	Destabilizing	0.975	D	0.609	neutral	None	None	None	None	N
R/S	0.9274	likely_pathogenic	0.897	pathogenic	-0.554	Destabilizing	0.892	D	0.654	neutral	N	0.46623904	None	None	N
R/T	0.9092	likely_pathogenic	0.8737	pathogenic	-0.349	Destabilizing	0.967	D	0.628	neutral	N	0.518228086	None	None	N
R/V	0.9471	likely_pathogenic	0.9302	pathogenic	-0.059	Destabilizing	0.975	D	0.727	prob.delet.	None	None	None	None	N
R/W	0.7419	likely_pathogenic	0.6829	pathogenic	-0.537	Destabilizing	0.999	D	0.795	deleterious	N	0.494904316	None	None	N
R/Y	0.926	likely_pathogenic	0.902	pathogenic	-0.163	Destabilizing	0.996	D	0.717	prob.delet.	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.