TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6482	19669;19670;19671	chr2:178728380;178728379;178728378	chr2:179593107;179593106;179593105
N2AB	6165	18718;18719;18720	chr2:178728380;178728379;178728378	chr2:179593107;179593106;179593105
N2A	5238	15937;15938;15939	chr2:178728380;178728379;178728378	chr2:179593107;179593106;179593105
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-49
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.3348
• 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	rs1560758702	None	0.989	N	0.349	0.414	0.331619326243	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0792	likely_benign	0.0746	benign	-0.649	Destabilizing	0.454	N	0.357	neutral	D	0.534904984	None	None	N
S/C	0.116	likely_benign	0.1161	benign	-0.392	Destabilizing	0.998	D	0.347	neutral	None	None	None	None	N
S/D	0.529	ambiguous	0.4653	ambiguous	0.619	Stabilizing	0.728	D	0.35	neutral	None	None	None	None	N
S/E	0.557	ambiguous	0.4787	ambiguous	0.579	Stabilizing	0.842	D	0.341	neutral	None	None	None	None	N
S/F	0.1247	likely_benign	0.1201	benign	-1.107	Destabilizing	0.949	D	0.403	neutral	None	None	None	None	N
S/G	0.1436	likely_benign	0.132	benign	-0.821	Destabilizing	0.842	D	0.329	neutral	None	None	None	None	N
S/H	0.3016	likely_benign	0.2793	benign	-1.211	Destabilizing	0.993	D	0.342	neutral	None	None	None	None	N
S/I	0.1131	likely_benign	0.1124	benign	-0.313	Destabilizing	0.728	D	0.338	neutral	None	None	None	None	N
S/K	0.5876	likely_pathogenic	0.4907	ambiguous	-0.247	Destabilizing	0.842	D	0.34	neutral	None	None	None	None	N
S/L	0.0798	likely_benign	0.082	benign	-0.313	Destabilizing	0.012	N	0.308	neutral	N	0.495202664	None	None	N
S/M	0.1712	likely_benign	0.1767	benign	-0.154	Destabilizing	0.949	D	0.351	neutral	None	None	None	None	N
S/N	0.1822	likely_benign	0.1823	benign	-0.121	Destabilizing	0.067	N	0.187	neutral	None	None	None	None	N
S/P	0.9124	likely_pathogenic	0.8471	pathogenic	-0.394	Destabilizing	0.989	D	0.349	neutral	N	0.495456154	None	None	N
S/Q	0.4503	ambiguous	0.4073	ambiguous	-0.264	Destabilizing	0.974	D	0.397	neutral	None	None	None	None	N
S/R	0.4641	ambiguous	0.3758	ambiguous	-0.167	Destabilizing	0.974	D	0.359	neutral	None	None	None	None	N
S/T	0.0648	likely_benign	0.0718	benign	-0.265	Destabilizing	0.801	D	0.377	neutral	N	0.513529634	None	None	N
S/V	0.1144	likely_benign	0.1176	benign	-0.394	Destabilizing	0.016	N	0.286	neutral	None	None	None	None	N
S/W	0.348	ambiguous	0.2688	benign	-1.052	Destabilizing	0.998	D	0.578	neutral	None	None	None	None	N
S/Y	0.151	likely_benign	0.1259	benign	-0.767	Destabilizing	0.974	D	0.399	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.