TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9134	27625;27626;27627	chr2:178712522;178712521;178712520	chr2:179577249;179577248;179577247
N2AB	8817	26674;26675;26676	chr2:178712522;178712521;178712520	chr2:179577249;179577248;179577247
N2A	7890	23893;23894;23895	chr2:178712522;178712521;178712520	chr2:179577249;179577248;179577247
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-77
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.2685
• 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/I	rs1023873134	None	0.001	N	0.348	0.113	0.425970041486	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
T/I	rs1023873134	None	0.001	N	0.348	0.113	0.425970041486	gnomAD-4.0.0	8.05683E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.01717E-05	0	1.60143E-05
T/R	rs1023873134	-0.262	0.484	N	0.641	0.226	0.508994031223	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
T/R	rs1023873134	-0.262	0.484	N	0.641	0.226	0.508994031223	gnomAD-4.0.0	6.84265E-07	None	None	None	None	N	None	0	2.23734E-05	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
T/A	0.0851	likely_benign	0.1054	benign	-1.254	Destabilizing	0.027	N	0.447	neutral	N	0.505219582	None	None	N
T/C	0.4192	ambiguous	0.5055	ambiguous	-0.795	Destabilizing	0.935	D	0.631	neutral	None	None	None	None	N
T/D	0.4023	ambiguous	0.4935	ambiguous	-0.76	Destabilizing	0.38	N	0.591	neutral	None	None	None	None	N
T/E	0.3327	likely_benign	0.3878	ambiguous	-0.622	Destabilizing	0.38	N	0.583	neutral	None	None	None	None	N
T/F	0.1962	likely_benign	0.2417	benign	-1.004	Destabilizing	0.235	N	0.682	prob.neutral	None	None	None	None	N
T/G	0.2806	likely_benign	0.3629	ambiguous	-1.615	Destabilizing	0.149	N	0.609	neutral	None	None	None	None	N
T/H	0.2623	likely_benign	0.3127	benign	-1.652	Destabilizing	0.935	D	0.687	prob.neutral	None	None	None	None	N
T/I	0.0979	likely_benign	0.127	benign	-0.328	Destabilizing	0.001	N	0.348	neutral	N	0.507337167	None	None	N
T/K	0.2592	likely_benign	0.2908	benign	-0.5	Destabilizing	0.117	N	0.58	neutral	N	0.47932106	None	None	N
T/L	0.0862	likely_benign	0.1028	benign	-0.328	Destabilizing	0.001	N	0.373	neutral	None	None	None	None	N
T/M	0.0856	likely_benign	0.0934	benign	-0.265	Destabilizing	0.235	N	0.646	neutral	None	None	None	None	N
T/N	0.1093	likely_benign	0.1425	benign	-0.869	Destabilizing	0.38	N	0.5	neutral	None	None	None	None	N
T/P	0.2753	likely_benign	0.3516	ambiguous	-0.606	Destabilizing	0.484	N	0.644	neutral	D	0.526192287	None	None	N
T/Q	0.2502	likely_benign	0.2851	benign	-0.822	Destabilizing	0.555	D	0.649	neutral	None	None	None	None	N
T/R	0.1974	likely_benign	0.2284	benign	-0.531	Destabilizing	0.484	N	0.641	neutral	N	0.467874702	None	None	N
T/S	0.1051	likely_benign	0.1343	benign	-1.222	Destabilizing	0.005	N	0.2	neutral	N	0.472723161	None	None	N
T/V	0.1022	likely_benign	0.1309	benign	-0.606	Destabilizing	0.035	N	0.465	neutral	None	None	None	None	N
T/W	0.6228	likely_pathogenic	0.6701	pathogenic	-0.978	Destabilizing	0.935	D	0.725	prob.delet.	None	None	None	None	N
T/Y	0.2582	likely_benign	0.3116	benign	-0.675	Destabilizing	0.555	D	0.697	prob.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.