TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27359	82300;82301;82302	chr2:178564057;178564056;178564055	chr2:179428784;179428783;179428782
N2AB	25718	77377;77378;77379	chr2:178564057;178564056;178564055	chr2:179428784;179428783;179428782
N2A	24791	74596;74597;74598	chr2:178564057;178564056;178564055	chr2:179428784;179428783;179428782
N2B	18294	55105;55106;55107	chr2:178564057;178564056;178564055	chr2:179428784;179428783;179428782
Novex-1	18419	55480;55481;55482	chr2:178564057;178564056;178564055	chr2:179428784;179428783;179428782
Novex-2	18486	55681;55682;55683	chr2:178564057;178564056;178564055	chr2:179428784;179428783;179428782
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-140
• Domain position: 82
• Structural Position: 168
• Q(SASA): 0.4374
• Predicted PPI site: I

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	rs1704715651	None	0.106	D	0.616	0.389	0.227934060464	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
S/P	rs1704715651	None	0.106	D	0.616	0.389	0.227934060464	gnomAD-4.0.0	6.57774E-06	None	None	None	None	I	None	2.41441E-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	0.0769	likely_benign	0.0781	benign	-0.29	Destabilizing	0.005	N	0.322	neutral	N	0.497595747	None	None	I
S/C	0.0932	likely_benign	0.0957	benign	-0.335	Destabilizing	0.612	D	0.541	neutral	D	0.540351624	None	None	I
S/D	0.2877	likely_benign	0.2927	benign	0.222	Stabilizing	0.072	N	0.411	neutral	None	None	None	None	I
S/E	0.3476	ambiguous	0.3555	ambiguous	0.22	Stabilizing	0.038	N	0.423	neutral	None	None	None	None	I
S/F	0.142	likely_benign	0.1523	benign	-0.531	Destabilizing	0.171	N	0.579	neutral	N	0.513346599	None	None	I
S/G	0.1115	likely_benign	0.1126	benign	-0.523	Destabilizing	0.031	N	0.415	neutral	None	None	None	None	I
S/H	0.2551	likely_benign	0.2597	benign	-0.959	Destabilizing	0.356	N	0.548	neutral	None	None	None	None	I
S/I	0.1119	likely_benign	0.1237	benign	0.21	Stabilizing	0.001	N	0.365	neutral	None	None	None	None	I
S/K	0.5396	ambiguous	0.537	ambiguous	-0.477	Destabilizing	0.038	N	0.417	neutral	None	None	None	None	I
S/L	0.0826	likely_benign	0.0842	benign	0.21	Stabilizing	0.007	N	0.421	neutral	None	None	None	None	I
S/M	0.12	likely_benign	0.126	benign	0.117	Stabilizing	0.003	N	0.259	neutral	None	None	None	None	I
S/N	0.0912	likely_benign	0.0911	benign	-0.445	Destabilizing	0.072	N	0.412	neutral	None	None	None	None	I
S/P	0.558	ambiguous	0.4184	ambiguous	0.079	Stabilizing	0.106	N	0.616	neutral	D	0.528323756	None	None	I
S/Q	0.3683	ambiguous	0.3658	ambiguous	-0.483	Destabilizing	0.003	N	0.289	neutral	None	None	None	None	I
S/R	0.4886	ambiguous	0.492	ambiguous	-0.443	Destabilizing	0.072	N	0.596	neutral	None	None	None	None	I
S/T	0.0617	likely_benign	0.0647	benign	-0.425	Destabilizing	None	N	0.137	neutral	N	0.485052167	None	None	I
S/V	0.1148	likely_benign	0.1219	benign	0.079	Stabilizing	0.016	N	0.446	neutral	None	None	None	None	I
S/W	0.2582	likely_benign	0.2804	benign	-0.625	Destabilizing	0.864	D	0.542	neutral	None	None	None	None	I
S/Y	0.1239	likely_benign	0.1374	benign	-0.297	Destabilizing	0.295	N	0.537	neutral	N	0.508004228	None	None	I

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.