TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24137	72634;72635;72636	chr2:178573723;178573722;178573721	chr2:179438450;179438449;179438448
N2AB	22496	67711;67712;67713	chr2:178573723;178573722;178573721	chr2:179438450;179438449;179438448
N2A	21569	64930;64931;64932	chr2:178573723;178573722;178573721	chr2:179438450;179438449;179438448
N2B	15072	45439;45440;45441	chr2:178573723;178573722;178573721	chr2:179438450;179438449;179438448
Novex-1	15197	45814;45815;45816	chr2:178573723;178573722;178573721	chr2:179438450;179438449;179438448
Novex-2	15264	46015;46016;46017	chr2:178573723;178573722;178573721	chr2:179438450;179438449;179438448
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: Fn3-63
• Domain position: 16
• Structural Position: 17
• Q(SASA): 0.1966
• 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/P	None	None	0.055	N	0.479	0.139	0.0762999501168	gnomAD-4.0.0	3.53603E-06	None	None	None	None	N	None	0	2.94221E-05	None	0	0	None	0	0	3.11896E-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
S/A	0.0531	likely_benign	0.062	benign	-0.513	Destabilizing	None	N	0.071	neutral	N	0.416741301	None	None	N
S/C	0.1002	likely_benign	0.0961	benign	-0.596	Destabilizing	None	N	0.292	neutral	None	None	None	None	N
S/D	0.4485	ambiguous	0.4875	ambiguous	-0.955	Destabilizing	0.016	N	0.29	neutral	None	None	None	None	N
S/E	0.4271	ambiguous	0.4683	ambiguous	-0.985	Destabilizing	None	N	0.131	neutral	None	None	None	None	N
S/F	0.2444	likely_benign	0.2956	benign	-0.886	Destabilizing	0.356	N	0.533	neutral	None	None	None	None	N
S/G	0.0956	likely_benign	0.0997	benign	-0.704	Destabilizing	0.016	N	0.3	neutral	None	None	None	None	N
S/H	0.4225	ambiguous	0.4397	ambiguous	-1.258	Destabilizing	0.628	D	0.509	neutral	None	None	None	None	N
S/I	0.1849	likely_benign	0.2387	benign	-0.122	Destabilizing	0.016	N	0.445	neutral	None	None	None	None	N
S/K	0.6832	likely_pathogenic	0.7307	pathogenic	-0.727	Destabilizing	0.031	N	0.288	neutral	None	None	None	None	N
S/L	0.1082	likely_benign	0.1322	benign	-0.122	Destabilizing	0.012	N	0.439	neutral	N	0.48607336	None	None	N
S/M	0.1711	likely_benign	0.1899	benign	0.233	Stabilizing	0.356	N	0.511	neutral	None	None	None	None	N
S/N	0.1808	likely_benign	0.1828	benign	-0.749	Destabilizing	0.072	N	0.336	neutral	None	None	None	None	N
S/P	0.259	likely_benign	0.3001	benign	-0.222	Destabilizing	0.055	N	0.479	neutral	N	0.497530313	None	None	N
S/Q	0.4629	ambiguous	0.4931	ambiguous	-1.063	Destabilizing	0.072	N	0.383	neutral	None	None	None	None	N
S/R	0.6152	likely_pathogenic	0.669	pathogenic	-0.486	Destabilizing	0.072	N	0.503	neutral	None	None	None	None	N
S/T	0.1098	likely_benign	0.1242	benign	-0.694	Destabilizing	None	N	0.111	neutral	D	0.523292763	None	None	N
S/V	0.1534	likely_benign	0.1973	benign	-0.222	Destabilizing	None	N	0.161	neutral	None	None	None	None	N
S/W	0.3708	ambiguous	0.4167	ambiguous	-0.879	Destabilizing	0.864	D	0.531	neutral	None	None	None	None	N
S/Y	0.2279	likely_benign	0.2547	benign	-0.58	Destabilizing	0.356	N	0.529	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.