TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33248	99967;99968;99969	chr2:178537465;178537464;178537463	chr2:179402192;179402191;179402190
N2AB	31607	95044;95045;95046	chr2:178537465;178537464;178537463	chr2:179402192;179402191;179402190
N2A	30680	92263;92264;92265	chr2:178537465;178537464;178537463	chr2:179402192;179402191;179402190
N2B	24183	72772;72773;72774	chr2:178537465;178537464;178537463	chr2:179402192;179402191;179402190
Novex-1	24308	73147;73148;73149	chr2:178537465;178537464;178537463	chr2:179402192;179402191;179402190
Novex-2	24375	73348;73349;73350	chr2:178537465;178537464;178537463	chr2:179402192;179402191;179402190
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-157
• Domain position: 46
• Structural Position: 130
• Q(SASA): 0.1532
• 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
T/S	rs1455373620	None	0.996	N	0.46	0.335	0.421060224861	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/S	rs1455373620	None	0.996	N	0.46	0.335	0.421060224861	gnomAD-4.0.0	6.57246E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.46994E-05	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
T/A	0.4455	ambiguous	0.4666	ambiguous	-0.916	Destabilizing	0.996	D	0.461	neutral	D	0.529576522	None	None	N
T/C	0.8884	likely_pathogenic	0.9106	pathogenic	-0.407	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
T/D	0.8121	likely_pathogenic	0.7949	pathogenic	-0.89	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
T/E	0.8745	likely_pathogenic	0.864	pathogenic	-0.769	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
T/F	0.9015	likely_pathogenic	0.918	pathogenic	-0.613	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
T/G	0.6929	likely_pathogenic	0.6682	pathogenic	-1.287	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
T/H	0.7862	likely_pathogenic	0.7745	pathogenic	-1.49	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
T/I	0.8751	likely_pathogenic	0.893	pathogenic	0.03	Stabilizing	1.0	D	0.671	neutral	N	0.491443682	None	None	N
T/K	0.7393	likely_pathogenic	0.711	pathogenic	-0.834	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
T/L	0.5647	likely_pathogenic	0.6121	pathogenic	0.03	Stabilizing	1.0	D	0.583	neutral	None	None	None	None	N
T/M	0.4329	ambiguous	0.4666	ambiguous	0.189	Stabilizing	1.0	D	0.67	neutral	None	None	None	None	N
T/N	0.4168	ambiguous	0.4016	ambiguous	-1.143	Destabilizing	1.0	D	0.682	prob.neutral	N	0.518108734	None	None	N
T/P	0.8131	likely_pathogenic	0.8114	pathogenic	-0.253	Destabilizing	1.0	D	0.675	neutral	D	0.530443313	None	None	N
T/Q	0.7562	likely_pathogenic	0.7474	pathogenic	-1.007	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
T/R	0.6818	likely_pathogenic	0.6614	pathogenic	-0.866	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
T/S	0.3288	likely_benign	0.3339	benign	-1.344	Destabilizing	0.996	D	0.46	neutral	N	0.513625634	None	None	N
T/V	0.7344	likely_pathogenic	0.7638	pathogenic	-0.253	Destabilizing	1.0	D	0.527	neutral	None	None	None	None	N
T/W	0.969	likely_pathogenic	0.9693	pathogenic	-0.768	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
T/Y	0.9087	likely_pathogenic	0.9173	pathogenic	-0.467	Destabilizing	1.0	D	0.743	deleterious	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.