TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35171	105736;105737;105738	chr2:178531104;178531103;178531102	chr2:179395831;179395830;179395829
N2AB	33530	100813;100814;100815	chr2:178531104;178531103;178531102	chr2:179395831;179395830;179395829
N2A	32603	98032;98033;98034	chr2:178531104;178531103;178531102	chr2:179395831;179395830;179395829
N2B	26106	78541;78542;78543	chr2:178531104;178531103;178531102	chr2:179395831;179395830;179395829
Novex-1	26231	78916;78917;78918	chr2:178531104;178531103;178531102	chr2:179395831;179395830;179395829
Novex-2	26298	79117;79118;79119	chr2:178531104;178531103;178531102	chr2:179395831;179395830;179395829
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-164
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.4748
• 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	rs774524898	-0.299	0.004	N	0.297	0.254	None	gnomAD-2.1.1	1.64534E-04	None	None	None	None	N	None	0	0	None	0	0	None	1.11104E-03	None	0	6.2E-05	0
T/I	rs774524898	-0.299	0.004	N	0.297	0.254	None	gnomAD-3.1.2	7.23E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	7.35E-05	1.24327E-03	0
T/I	rs774524898	-0.299	0.004	N	0.297	0.254	None	gnomAD-4.0.0	1.01619E-04	None	None	None	None	N	None	0	0	None	0	0	None	0	3.28731E-04	5.00049E-05	1.08691E-03	6.40369E-05

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	0.0714	likely_benign	0.0667	benign	-0.314	Destabilizing	None	N	0.098	neutral	N	0.449267512	None	None	N
T/C	0.4434	ambiguous	0.3904	ambiguous	-0.185	Destabilizing	0.177	N	0.317	neutral	None	None	None	None	N
T/D	0.2645	likely_benign	0.2313	benign	0.211	Stabilizing	0.029	N	0.315	neutral	None	None	None	None	N
T/E	0.2355	likely_benign	0.2032	benign	0.122	Stabilizing	0.015	N	0.297	neutral	None	None	None	None	N
T/F	0.2124	likely_benign	0.1881	benign	-0.924	Destabilizing	0.096	N	0.339	neutral	None	None	None	None	N
T/G	0.1837	likely_benign	0.1647	benign	-0.406	Destabilizing	0.006	N	0.265	neutral	None	None	None	None	N
T/H	0.2123	likely_benign	0.1798	benign	-0.759	Destabilizing	0.177	N	0.307	neutral	None	None	None	None	N
T/I	0.1659	likely_benign	0.1464	benign	-0.196	Destabilizing	0.004	N	0.297	neutral	N	0.486555384	None	None	N
T/K	0.184	likely_benign	0.1549	benign	-0.241	Destabilizing	0.015	N	0.295	neutral	None	None	None	None	N
T/L	0.1076	likely_benign	0.1009	benign	-0.196	Destabilizing	0.006	N	0.285	neutral	None	None	None	None	N
T/M	0.1135	likely_benign	0.1069	benign	0.032	Stabilizing	0.096	N	0.316	neutral	None	None	None	None	N
T/N	0.1	likely_benign	0.0905	benign	-0.007	Destabilizing	0.011	N	0.155	neutral	N	0.501235127	None	None	N
T/P	0.0873	likely_benign	0.0834	benign	-0.209	Destabilizing	0.044	N	0.358	neutral	N	0.468565348	None	None	N
T/Q	0.1949	likely_benign	0.1711	benign	-0.247	Destabilizing	0.096	N	0.359	neutral	None	None	None	None	N
T/R	0.1411	likely_benign	0.1209	benign	-0.019	Destabilizing	0.029	N	0.377	neutral	None	None	None	None	N
T/S	0.0847	likely_benign	0.079	benign	-0.204	Destabilizing	None	N	0.14	neutral	N	0.411015768	None	None	N
T/V	0.1336	likely_benign	0.1202	benign	-0.209	Destabilizing	None	N	0.091	neutral	None	None	None	None	N
T/W	0.5754	likely_pathogenic	0.5148	ambiguous	-0.948	Destabilizing	0.712	D	0.321	neutral	None	None	None	None	N
T/Y	0.2556	likely_benign	0.224	benign	-0.644	Destabilizing	0.177	N	0.328	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.