TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20702	62329;62330;62331	chr2:178589621;178589620;178589619	chr2:179454348;179454347;179454346
N2AB	19061	57406;57407;57408	chr2:178589621;178589620;178589619	chr2:179454348;179454347;179454346
N2A	18134	54625;54626;54627	chr2:178589621;178589620;178589619	chr2:179454348;179454347;179454346
N2B	11637	35134;35135;35136	chr2:178589621;178589620;178589619	chr2:179454348;179454347;179454346
Novex-1	11762	35509;35510;35511	chr2:178589621;178589620;178589619	chr2:179454348;179454347;179454346
Novex-2	11829	35710;35711;35712	chr2:178589621;178589620;178589619	chr2:179454348;179454347;179454346
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: Fn3-38
• Domain position: 35
• Structural Position: 37
• Q(SASA): 0.0793
• 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/T	None	None	0.103	N	0.366	0.071	0.210429274316	gnomAD-4.0.0	6.84416E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99682E-07	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	0.1003	likely_benign	0.1271	benign	-0.708	Destabilizing	0.64	D	0.515	neutral	N	0.437327217	None	None	N
S/C	0.1176	likely_benign	0.1355	benign	-0.652	Destabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	N
S/D	0.886	likely_pathogenic	0.8126	pathogenic	-1.528	Destabilizing	0.919	D	0.606	neutral	None	None	None	None	N
S/E	0.9046	likely_pathogenic	0.8552	pathogenic	-1.407	Destabilizing	0.919	D	0.602	neutral	None	None	None	None	N
S/F	0.5052	ambiguous	0.4428	ambiguous	-0.514	Destabilizing	0.988	D	0.743	deleterious	None	None	None	None	N
S/G	0.1583	likely_benign	0.155	benign	-1.052	Destabilizing	0.034	N	0.185	neutral	None	None	None	None	N
S/H	0.7042	likely_pathogenic	0.6099	pathogenic	-1.46	Destabilizing	0.076	N	0.568	neutral	None	None	None	None	N
S/I	0.6241	likely_pathogenic	0.5843	pathogenic	0.137	Stabilizing	0.976	D	0.752	deleterious	None	None	None	None	N
S/K	0.9741	likely_pathogenic	0.968	pathogenic	-0.745	Destabilizing	0.919	D	0.614	neutral	None	None	None	None	N
S/L	0.2862	likely_benign	0.2559	benign	0.137	Stabilizing	0.811	D	0.73	prob.delet.	N	0.518558947	None	None	N
S/M	0.3736	ambiguous	0.3565	ambiguous	0.226	Stabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	N
S/N	0.4254	ambiguous	0.3611	ambiguous	-1.215	Destabilizing	0.919	D	0.591	neutral	None	None	None	None	N
S/P	0.9805	likely_pathogenic	0.9802	pathogenic	-0.11	Destabilizing	0.984	D	0.717	prob.delet.	N	0.518905663	None	None	N
S/Q	0.8136	likely_pathogenic	0.7798	pathogenic	-1.131	Destabilizing	0.988	D	0.634	neutral	None	None	None	None	N
S/R	0.9475	likely_pathogenic	0.9345	pathogenic	-0.879	Destabilizing	0.976	D	0.716	prob.delet.	None	None	None	None	N
S/T	0.1363	likely_benign	0.1354	benign	-0.919	Destabilizing	0.103	N	0.366	neutral	N	0.469650279	None	None	N
S/V	0.507	ambiguous	0.5076	ambiguous	-0.11	Destabilizing	0.851	D	0.734	prob.delet.	None	None	None	None	N
S/W	0.7158	likely_pathogenic	0.6581	pathogenic	-0.738	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
S/Y	0.4643	ambiguous	0.4027	ambiguous	-0.362	Destabilizing	0.976	D	0.755	deleterious	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.