TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30377	91354;91355;91356	chr2:178551771;178551770;178551769	chr2:179416498;179416497;179416496
N2AB	28736	86431;86432;86433	chr2:178551771;178551770;178551769	chr2:179416498;179416497;179416496
N2A	27809	83650;83651;83652	chr2:178551771;178551770;178551769	chr2:179416498;179416497;179416496
N2B	21312	64159;64160;64161	chr2:178551771;178551770;178551769	chr2:179416498;179416497;179416496
Novex-1	21437	64534;64535;64536	chr2:178551771;178551770;178551769	chr2:179416498;179416497;179416496
Novex-2	21504	64735;64736;64737	chr2:178551771;178551770;178551769	chr2:179416498;179416497;179416496
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: Fn3-109
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.5022
• 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/L	None	None	0.193	N	0.249	0.215	0.448597761117	gnomAD-4.0.0	6.84194E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99455E-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	0.0662	likely_benign	0.0685	benign	-0.167	Destabilizing	0.001	N	0.068	neutral	N	0.472671941	None	None	N
S/C	0.0786	likely_benign	0.0828	benign	-0.143	Destabilizing	0.944	D	0.283	neutral	None	None	None	None	N
S/D	0.4248	ambiguous	0.3993	ambiguous	-0.034	Destabilizing	0.388	N	0.178	neutral	None	None	None	None	N
S/E	0.4851	ambiguous	0.4479	ambiguous	-0.132	Destabilizing	0.388	N	0.172	neutral	None	None	None	None	N
S/F	0.1049	likely_benign	0.1147	benign	-0.778	Destabilizing	0.818	D	0.381	neutral	None	None	None	None	N
S/G	0.0836	likely_benign	0.0851	benign	-0.264	Destabilizing	0.116	N	0.165	neutral	None	None	None	None	N
S/H	0.2417	likely_benign	0.243	benign	-0.665	Destabilizing	0.005	N	0.157	neutral	None	None	None	None	N
S/I	0.0826	likely_benign	0.0832	benign	-0.041	Destabilizing	0.527	D	0.378	neutral	None	None	None	None	N
S/K	0.5345	ambiguous	0.5047	ambiguous	-0.447	Destabilizing	0.388	N	0.183	neutral	None	None	None	None	N
S/L	0.0647	likely_benign	0.068	benign	-0.041	Destabilizing	0.193	N	0.249	neutral	N	0.48350501	None	None	N
S/M	0.0977	likely_benign	0.1045	benign	0.044	Stabilizing	0.818	D	0.285	neutral	None	None	None	None	N
S/N	0.0943	likely_benign	0.0969	benign	-0.069	Destabilizing	0.388	N	0.211	neutral	None	None	None	None	N
S/P	0.5123	ambiguous	0.506	ambiguous	-0.055	Destabilizing	0.773	D	0.321	neutral	N	0.504837501	None	None	N
S/Q	0.3351	likely_benign	0.3327	benign	-0.312	Destabilizing	0.818	D	0.293	neutral	None	None	None	None	N
S/R	0.4998	ambiguous	0.4734	ambiguous	-0.181	Destabilizing	0.69	D	0.33	neutral	None	None	None	None	N
S/T	0.0575	likely_benign	0.0601	benign	-0.151	Destabilizing	0.001	N	0.07	neutral	N	0.395827311	None	None	N
S/V	0.0844	likely_benign	0.087	benign	-0.055	Destabilizing	0.241	N	0.289	neutral	None	None	None	None	N
S/W	0.2712	likely_benign	0.2638	benign	-0.857	Destabilizing	0.981	D	0.422	neutral	None	None	None	None	N
S/Y	0.1271	likely_benign	0.1264	benign	-0.558	Destabilizing	0.69	D	0.385	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.