TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18900	56923;56924;56925	chr2:178599012;178599011;178599010	chr2:179463739;179463738;179463737
N2AB	17259	52000;52001;52002	chr2:178599012;178599011;178599010	chr2:179463739;179463738;179463737
N2A	16332	49219;49220;49221	chr2:178599012;178599011;178599010	chr2:179463739;179463738;179463737
N2B	9835	29728;29729;29730	chr2:178599012;178599011;178599010	chr2:179463739;179463738;179463737
Novex-1	9960	30103;30104;30105	chr2:178599012;178599011;178599010	chr2:179463739;179463738;179463737
Novex-2	10027	30304;30305;30306	chr2:178599012;178599011;178599010	chr2:179463739;179463738;179463737
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Fn3-25
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1189
• 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/C	rs1256105535	None	1.0	N	0.7	0.443	0.536661227952	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93751E-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	0.1147	likely_benign	0.1236	benign	-0.47	Destabilizing	0.973	D	0.419	neutral	N	0.509483677	None	None	N
S/C	0.116	likely_benign	0.1225	benign	-0.872	Destabilizing	1.0	D	0.7	prob.neutral	N	0.486561248	None	None	N
S/D	0.7326	likely_pathogenic	0.8056	pathogenic	-1.863	Destabilizing	0.996	D	0.522	neutral	None	None	None	None	N
S/E	0.7131	likely_pathogenic	0.7644	pathogenic	-1.821	Destabilizing	0.999	D	0.529	neutral	None	None	None	None	N
S/F	0.2535	likely_benign	0.2673	benign	-0.898	Destabilizing	0.999	D	0.725	prob.delet.	N	0.487130679	None	None	N
S/G	0.1461	likely_benign	0.1662	benign	-0.69	Destabilizing	0.134	N	0.247	neutral	None	None	None	None	N
S/H	0.4796	ambiguous	0.4416	ambiguous	-1.226	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
S/I	0.4761	ambiguous	0.5325	ambiguous	0.011	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
S/K	0.9337	likely_pathogenic	0.9388	pathogenic	-0.645	Destabilizing	0.996	D	0.542	neutral	None	None	None	None	N
S/L	0.2386	likely_benign	0.3054	benign	0.011	Stabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
S/M	0.2471	likely_benign	0.2975	benign	0.22	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
S/N	0.2969	likely_benign	0.3637	ambiguous	-1.087	Destabilizing	0.996	D	0.536	neutral	None	None	None	None	N
S/P	0.9967	likely_pathogenic	0.997	pathogenic	-0.118	Destabilizing	0.999	D	0.731	prob.delet.	D	0.534695495	None	None	N
S/Q	0.6868	likely_pathogenic	0.6682	pathogenic	-1.309	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
S/R	0.8999	likely_pathogenic	0.9065	pathogenic	-0.492	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
S/T	0.1109	likely_benign	0.1311	benign	-0.81	Destabilizing	0.994	D	0.479	neutral	N	0.487009462	None	None	N
S/V	0.4202	ambiguous	0.462	ambiguous	-0.118	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
S/W	0.5972	likely_pathogenic	0.5661	pathogenic	-1.052	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
S/Y	0.2861	likely_benign	0.2597	benign	-0.624	Destabilizing	0.999	D	0.73	prob.delet.	N	0.482166702	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.