TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16150	48673;48674;48675	chr2:178615653;178615652;178615651	chr2:179480380;179480379;179480378
N2AB	14509	43750;43751;43752	chr2:178615653;178615652;178615651	chr2:179480380;179480379;179480378
N2A	13582	40969;40970;40971	chr2:178615653;178615652;178615651	chr2:179480380;179480379;179480378
N2B	7085	21478;21479;21480	chr2:178615653;178615652;178615651	chr2:179480380;179480379;179480378
Novex-1	7210	21853;21854;21855	chr2:178615653;178615652;178615651	chr2:179480380;179480379;179480378
Novex-2	7277	22054;22055;22056	chr2:178615653;178615652;178615651	chr2:179480380;179480379;179480378
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: Fn3-4
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.2566
• 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	0.657	N	0.531	0.322	0.450343601259	gnomAD-4.0.0	6.84768E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00075E-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	0.0895	likely_benign	0.1007	benign	-0.451	Destabilizing	0.012	N	0.228	neutral	N	0.470177862	None	None	N
S/C	0.1501	likely_benign	0.171	benign	-0.315	Destabilizing	0.993	D	0.615	neutral	None	None	None	None	N
S/D	0.5803	likely_pathogenic	0.5683	pathogenic	-0.182	Destabilizing	0.911	D	0.623	neutral	None	None	None	None	N
S/E	0.6624	likely_pathogenic	0.6414	pathogenic	-0.258	Destabilizing	0.835	D	0.626	neutral	None	None	None	None	N
S/F	0.3023	likely_benign	0.3419	ambiguous	-0.878	Destabilizing	0.973	D	0.736	deleterious	None	None	None	None	N
S/G	0.1237	likely_benign	0.1445	benign	-0.61	Destabilizing	0.717	D	0.418	neutral	None	None	None	None	N
S/H	0.4924	ambiguous	0.5155	ambiguous	-1.182	Destabilizing	0.998	D	0.603	neutral	None	None	None	None	N
S/I	0.2498	likely_benign	0.2883	benign	-0.156	Destabilizing	0.947	D	0.739	deleterious	None	None	None	None	N
S/K	0.8145	likely_pathogenic	0.8066	pathogenic	-0.721	Destabilizing	0.835	D	0.616	neutral	None	None	None	None	N
S/L	0.1307	likely_benign	0.1504	benign	-0.156	Destabilizing	0.657	D	0.531	neutral	N	0.470830879	None	None	N
S/M	0.219	likely_benign	0.2574	benign	0.147	Stabilizing	0.998	D	0.597	neutral	None	None	None	None	N
S/N	0.1841	likely_benign	0.2131	benign	-0.426	Destabilizing	0.973	D	0.639	neutral	None	None	None	None	N
S/P	0.5977	likely_pathogenic	0.6155	pathogenic	-0.224	Destabilizing	0.964	D	0.637	neutral	N	0.471981797	None	None	N
S/Q	0.5835	likely_pathogenic	0.5921	pathogenic	-0.687	Destabilizing	0.973	D	0.635	neutral	None	None	None	None	N
S/R	0.7639	likely_pathogenic	0.7483	pathogenic	-0.51	Destabilizing	0.973	D	0.649	prob.neutral	None	None	None	None	N
S/T	0.0959	likely_benign	0.1114	benign	-0.484	Destabilizing	0.792	D	0.433	neutral	N	0.457716442	None	None	N
S/V	0.2175	likely_benign	0.2538	benign	-0.224	Destabilizing	0.899	D	0.547	neutral	None	None	None	None	N
S/W	0.4868	ambiguous	0.4938	ambiguous	-0.869	Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
S/Y	0.3058	likely_benign	0.3176	benign	-0.617	Destabilizing	0.991	D	0.719	prob.delet.	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.