TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7805	23638;23639;23640	chr2:178720229;178720228;178720227	chr2:179584956;179584955;179584954
N2AB	7488	22687;22688;22689	chr2:178720229;178720228;178720227	chr2:179584956;179584955;179584954
N2A	6561	19906;19907;19908	chr2:178720229;178720228;178720227	chr2:179584956;179584955;179584954
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-63
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.3296
• 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
S/A	rs369062299	-0.573	None	D	0.085	0.172	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	0	0	0
S/A	rs369062299	-0.573	None	D	0.085	0.172	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
S/A	rs369062299	-0.573	None	D	0.085	0.172	None	gnomAD-4.0.0	2.0299E-06	None	None	None	None	N	None	3.49455E-05	0	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
S/A	0.0835	likely_benign	0.0815	benign	-0.351	Destabilizing	None	N	0.085	neutral	D	0.525861426	None	None	N
S/C	0.1637	likely_benign	0.1521	benign	-0.231	Destabilizing	0.986	D	0.4	neutral	None	None	None	None	N
S/D	0.4019	ambiguous	0.3579	ambiguous	0.381	Stabilizing	0.003	N	0.147	neutral	None	None	None	None	N
S/E	0.4236	ambiguous	0.3943	ambiguous	0.295	Stabilizing	0.195	N	0.307	neutral	None	None	None	None	N
S/F	0.2239	likely_benign	0.2029	benign	-0.916	Destabilizing	0.957	D	0.47	neutral	None	None	None	None	N
S/G	0.1374	likely_benign	0.1298	benign	-0.473	Destabilizing	0.244	N	0.329	neutral	None	None	None	None	N
S/H	0.3317	likely_benign	0.3054	benign	-0.981	Destabilizing	0.957	D	0.411	neutral	None	None	None	None	N
S/I	0.1893	likely_benign	0.174	benign	-0.16	Destabilizing	0.611	D	0.425	neutral	None	None	None	None	N
S/K	0.5468	ambiguous	0.5023	ambiguous	-0.359	Destabilizing	0.759	D	0.303	neutral	None	None	None	None	N
S/L	0.1326	likely_benign	0.1272	benign	-0.16	Destabilizing	0.329	N	0.401	neutral	N	0.503329739	None	None	N
S/M	0.2349	likely_benign	0.2255	benign	0.054	Stabilizing	0.957	D	0.411	neutral	None	None	None	None	N
S/N	0.1486	likely_benign	0.1315	benign	-0.089	Destabilizing	0.001	N	0.175	neutral	None	None	None	None	N
S/P	0.3982	ambiguous	0.3759	ambiguous	-0.194	Destabilizing	0.563	D	0.437	neutral	N	0.515611097	None	None	N
S/Q	0.4309	ambiguous	0.4074	ambiguous	-0.317	Destabilizing	0.957	D	0.378	neutral	None	None	None	None	N
S/R	0.4401	ambiguous	0.4042	ambiguous	-0.211	Destabilizing	0.957	D	0.428	neutral	None	None	None	None	N
S/T	0.077	likely_benign	0.074	benign	-0.216	Destabilizing	0.001	N	0.123	neutral	N	0.447670001	None	None	N
S/V	0.1707	likely_benign	0.1622	benign	-0.194	Destabilizing	0.016	N	0.309	neutral	None	None	None	None	N
S/W	0.3951	ambiguous	0.3788	ambiguous	-0.919	Destabilizing	0.996	D	0.539	neutral	None	None	None	None	N
S/Y	0.1972	likely_benign	0.1833	benign	-0.627	Destabilizing	0.986	D	0.473	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.