TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18798	56617;56618;56619	chr2:178599401;178599400;178599399	chr2:179464128;179464127;179464126
N2AB	17157	51694;51695;51696	chr2:178599401;178599400;178599399	chr2:179464128;179464127;179464126
N2A	16230	48913;48914;48915	chr2:178599401;178599400;178599399	chr2:179464128;179464127;179464126
N2B	9733	29422;29423;29424	chr2:178599401;178599400;178599399	chr2:179464128;179464127;179464126
Novex-1	9858	29797;29798;29799	chr2:178599401;178599400;178599399	chr2:179464128;179464127;179464126
Novex-2	9925	29998;29999;30000	chr2:178599401;178599400;178599399	chr2:179464128;179464127;179464126
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: Fn3-24
• Domain position: 15
• Structural Position: 16
• Q(SASA): 0.2167
• 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	rs2052673581	None	0.001	N	0.14	0.167	0.359557344763	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/L	rs2052673581	None	0.001	N	0.14	0.167	0.359557344763	gnomAD-4.0.0	6.57678E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47067E-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
S/A	0.1	likely_benign	0.1059	benign	-0.404	Destabilizing	0.08	N	0.273	neutral	N	0.469324992	None	None	N
S/C	0.1251	likely_benign	0.1332	benign	-0.515	Destabilizing	0.965	D	0.349	neutral	None	None	None	None	N
S/D	0.4499	ambiguous	0.5358	ambiguous	-1.337	Destabilizing	0.561	D	0.266	neutral	None	None	None	None	N
S/E	0.5908	likely_pathogenic	0.6497	pathogenic	-1.323	Destabilizing	0.561	D	0.225	neutral	None	None	None	None	N
S/F	0.2069	likely_benign	0.237	benign	-0.628	Destabilizing	0.002	N	0.142	neutral	None	None	None	None	N
S/G	0.1008	likely_benign	0.1173	benign	-0.659	Destabilizing	0.345	N	0.221	neutral	None	None	None	None	N
S/H	0.3207	likely_benign	0.3547	ambiguous	-1.27	Destabilizing	0.965	D	0.343	neutral	None	None	None	None	N
S/I	0.2634	likely_benign	0.3152	benign	0.164	Stabilizing	0.209	N	0.313	neutral	None	None	None	None	N
S/K	0.6165	likely_pathogenic	0.6784	pathogenic	-0.839	Destabilizing	0.561	D	0.231	neutral	None	None	None	None	N
S/L	0.1128	likely_benign	0.1253	benign	0.164	Stabilizing	0.001	N	0.14	neutral	N	0.474250809	None	None	N
S/M	0.1862	likely_benign	0.1991	benign	0.49	Stabilizing	0.047	N	0.235	neutral	None	None	None	None	N
S/N	0.157	likely_benign	0.1873	benign	-1.037	Destabilizing	0.561	D	0.278	neutral	None	None	None	None	N
S/P	0.8801	likely_pathogenic	0.9293	pathogenic	0.009	Stabilizing	0.662	D	0.401	neutral	N	0.483982992	None	None	N
S/Q	0.4741	ambiguous	0.5157	ambiguous	-1.217	Destabilizing	0.722	D	0.347	neutral	None	None	None	None	N
S/R	0.5295	ambiguous	0.6093	pathogenic	-0.691	Destabilizing	0.561	D	0.407	neutral	None	None	None	None	N
S/T	0.0733	likely_benign	0.0785	benign	-0.829	Destabilizing	0.001	N	0.082	neutral	N	0.373678383	None	None	N
S/V	0.2399	likely_benign	0.274	benign	0.009	Stabilizing	0.209	N	0.313	neutral	None	None	None	None	N
S/W	0.3875	ambiguous	0.4455	ambiguous	-0.744	Destabilizing	0.991	D	0.4	neutral	None	None	None	None	N
S/Y	0.2158	likely_benign	0.2318	benign	-0.405	Destabilizing	0.39	N	0.385	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.