TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5979	18160;18161;18162	chr2:178730598;178730597;178730596	chr2:179595325;179595324;179595323
N2AB	5662	17209;17210;17211	chr2:178730598;178730597;178730596	chr2:179595325;179595324;179595323
N2A	4735	14428;14429;14430	chr2:178730598;178730597;178730596	chr2:179595325;179595324;179595323
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-43
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.3152
• 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/N	rs1188866592	None	0.002	N	0.079	0.154	0.187945064343	gnomAD-4.0.0	1.5916E-06	None	None	None	None	N	None	0	0	None	0	2.77331E-05	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	0.0964	likely_benign	0.0951	benign	-0.856	Destabilizing	0.495	N	0.283	neutral	None	None	None	None	N
S/C	0.1141	likely_benign	0.1194	benign	-0.693	Destabilizing	0.013	N	0.209	neutral	N	0.515259157	None	None	N
S/D	0.2964	likely_benign	0.3468	ambiguous	-0.766	Destabilizing	0.543	D	0.307	neutral	None	None	None	None	N
S/E	0.4439	ambiguous	0.4871	ambiguous	-0.665	Destabilizing	0.704	D	0.32	neutral	None	None	None	None	N
S/F	0.2057	likely_benign	0.2128	benign	-0.724	Destabilizing	0.893	D	0.513	neutral	None	None	None	None	N
S/G	0.0847	likely_benign	0.0866	benign	-1.19	Destabilizing	0.27	N	0.318	neutral	N	0.500509036	None	None	N
S/H	0.2078	likely_benign	0.2288	benign	-1.484	Destabilizing	0.944	D	0.445	neutral	None	None	None	None	N
S/I	0.1496	likely_benign	0.1658	benign	-0.042	Destabilizing	0.473	N	0.487	neutral	D	0.523594699	None	None	N
S/K	0.4185	ambiguous	0.4841	ambiguous	-0.529	Destabilizing	0.329	N	0.319	neutral	None	None	None	None	N
S/L	0.1124	likely_benign	0.1112	benign	-0.042	Destabilizing	0.007	N	0.25	neutral	None	None	None	None	N
S/M	0.2012	likely_benign	0.2089	benign	0.001	Stabilizing	0.893	D	0.445	neutral	None	None	None	None	N
S/N	0.0806	likely_benign	0.0963	benign	-0.831	Destabilizing	0.002	N	0.079	neutral	N	0.462044808	None	None	N
S/P	0.3003	likely_benign	0.2945	benign	-0.279	Destabilizing	0.981	D	0.453	neutral	None	None	None	None	N
S/Q	0.3567	ambiguous	0.3807	ambiguous	-0.82	Destabilizing	0.893	D	0.394	neutral	None	None	None	None	N
S/R	0.3352	likely_benign	0.3719	ambiguous	-0.618	Destabilizing	0.006	N	0.219	neutral	N	0.500043049	None	None	N
S/T	0.0803	likely_benign	0.0851	benign	-0.717	Destabilizing	0.425	N	0.363	neutral	N	0.495271947	None	None	N
S/V	0.1847	likely_benign	0.196	benign	-0.279	Destabilizing	0.543	D	0.499	neutral	None	None	None	None	N
S/W	0.3348	likely_benign	0.3474	ambiguous	-0.774	Destabilizing	0.995	D	0.561	neutral	None	None	None	None	N
S/Y	0.158	likely_benign	0.1727	benign	-0.443	Destabilizing	0.981	D	0.519	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.