TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20444	61555;61556;61557	chr2:178590395;178590394;178590393	chr2:179455122;179455121;179455120
N2AB	18803	56632;56633;56634	chr2:178590395;178590394;178590393	chr2:179455122;179455121;179455120
N2A	17876	53851;53852;53853	chr2:178590395;178590394;178590393	chr2:179455122;179455121;179455120
N2B	11379	34360;34361;34362	chr2:178590395;178590394;178590393	chr2:179455122;179455121;179455120
Novex-1	11504	34735;34736;34737	chr2:178590395;178590394;178590393	chr2:179455122;179455121;179455120
Novex-2	11571	34936;34937;34938	chr2:178590395;178590394;178590393	chr2:179455122;179455121;179455120
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-36
• Domain position: 74
• Structural Position: 105
• Q(SASA): 0.4496
• 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/S	rs758056865	-2.1	0.811	N	0.549	0.238	0.307016933798	gnomAD-2.1.1	4.19E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.2E-06	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	0.5475	ambiguous	0.5138	ambiguous	-1.461	Destabilizing	0.132	N	0.351	neutral	None	None	None	None	N
R/C	0.1671	likely_benign	0.1599	benign	-1.454	Destabilizing	0.999	D	0.726	prob.delet.	None	None	None	None	N
R/D	0.8517	likely_pathogenic	0.8175	pathogenic	-0.326	Destabilizing	0.976	D	0.649	neutral	None	None	None	None	N
R/E	0.5917	likely_pathogenic	0.5408	ambiguous	-0.148	Destabilizing	0.851	D	0.559	neutral	None	None	None	None	N
R/F	0.599	likely_pathogenic	0.557	ambiguous	-0.97	Destabilizing	0.996	D	0.732	prob.delet.	None	None	None	None	N
R/G	0.4874	ambiguous	0.4296	ambiguous	-1.817	Destabilizing	0.896	D	0.576	neutral	N	0.487346672	None	None	N
R/H	0.1077	likely_benign	0.1043	benign	-1.823	Destabilizing	0.996	D	0.619	neutral	None	None	None	None	N
R/I	0.2713	likely_benign	0.2484	benign	-0.465	Destabilizing	0.984	D	0.719	prob.delet.	N	0.492737782	None	None	N
R/K	0.1153	likely_benign	0.1068	benign	-1.231	Destabilizing	0.011	N	0.281	neutral	N	0.439268657	None	None	N
R/L	0.2593	likely_benign	0.2496	benign	-0.465	Destabilizing	0.919	D	0.565	neutral	None	None	None	None	N
R/M	0.3382	likely_benign	0.3158	benign	-0.873	Destabilizing	0.999	D	0.643	neutral	None	None	None	None	N
R/N	0.6607	likely_pathogenic	0.6124	pathogenic	-0.847	Destabilizing	0.976	D	0.583	neutral	None	None	None	None	N
R/P	0.9561	likely_pathogenic	0.9425	pathogenic	-0.78	Destabilizing	0.988	D	0.69	prob.neutral	None	None	None	None	N
R/Q	0.124	likely_benign	0.1196	benign	-0.918	Destabilizing	0.976	D	0.612	neutral	None	None	None	None	N
R/S	0.5717	likely_pathogenic	0.5346	ambiguous	-1.803	Destabilizing	0.811	D	0.549	neutral	N	0.491004199	None	None	N
R/T	0.2913	likely_benign	0.2673	benign	-1.412	Destabilizing	0.896	D	0.528	neutral	N	0.479728413	None	None	N
R/V	0.3519	ambiguous	0.3381	benign	-0.78	Destabilizing	0.976	D	0.633	neutral	None	None	None	None	N
R/W	0.2376	likely_benign	0.2195	benign	-0.446	Destabilizing	0.999	D	0.728	prob.delet.	None	None	None	None	N
R/Y	0.452	ambiguous	0.4086	ambiguous	-0.247	Destabilizing	0.996	D	0.707	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.