TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32039	96340;96341;96342	chr2:178544029;178544028;178544027	chr2:179408756;179408755;179408754
N2AB	30398	91417;91418;91419	chr2:178544029;178544028;178544027	chr2:179408756;179408755;179408754
N2A	29471	88636;88637;88638	chr2:178544029;178544028;178544027	chr2:179408756;179408755;179408754
N2B	22974	69145;69146;69147	chr2:178544029;178544028;178544027	chr2:179408756;179408755;179408754
Novex-1	23099	69520;69521;69522	chr2:178544029;178544028;178544027	chr2:179408756;179408755;179408754
Novex-2	23166	69721;69722;69723	chr2:178544029;178544028;178544027	chr2:179408756;179408755;179408754
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-153
• Domain position: 23
• Structural Position: 38
• Q(SASA): 0.4248
• 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/T	None	None	0.079	N	0.161	0.145	0.218112801441	gnomAD-4.0.0	1.59154E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85883E-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	0.0808	likely_benign	0.076	benign	-0.192	Destabilizing	0.76	D	0.358	neutral	N	0.464930397	None	None	N
S/C	0.1064	likely_benign	0.1012	benign	-0.383	Destabilizing	0.999	D	0.561	neutral	D	0.533195617	None	None	N
S/D	0.5901	likely_pathogenic	0.523	ambiguous	0.131	Stabilizing	0.953	D	0.41	neutral	None	None	None	None	N
S/E	0.6308	likely_pathogenic	0.5534	ambiguous	0.024	Stabilizing	0.953	D	0.416	neutral	None	None	None	None	N
S/F	0.1783	likely_benign	0.1506	benign	-0.973	Destabilizing	0.991	D	0.647	neutral	N	0.511030833	None	None	N
S/G	0.119	likely_benign	0.1061	benign	-0.217	Destabilizing	0.953	D	0.37	neutral	None	None	None	None	N
S/H	0.2862	likely_benign	0.2614	benign	-0.588	Destabilizing	0.999	D	0.546	neutral	None	None	None	None	N
S/I	0.1555	likely_benign	0.1381	benign	-0.255	Destabilizing	0.986	D	0.641	neutral	None	None	None	None	N
S/K	0.4999	ambiguous	0.4364	ambiguous	-0.322	Destabilizing	0.953	D	0.413	neutral	None	None	None	None	N
S/L	0.0959	likely_benign	0.0851	benign	-0.255	Destabilizing	0.91	D	0.5	neutral	None	None	None	None	N
S/M	0.1643	likely_benign	0.1589	benign	-0.214	Destabilizing	0.999	D	0.549	neutral	None	None	None	None	N
S/N	0.1593	likely_benign	0.1396	benign	-0.12	Destabilizing	0.953	D	0.417	neutral	None	None	None	None	N
S/P	0.9055	likely_pathogenic	0.8783	pathogenic	-0.212	Destabilizing	0.991	D	0.554	neutral	N	0.486772874	None	None	N
S/Q	0.4406	ambiguous	0.4051	ambiguous	-0.31	Destabilizing	0.993	D	0.519	neutral	None	None	None	None	N
S/R	0.4262	ambiguous	0.3652	ambiguous	-0.156	Destabilizing	0.986	D	0.558	neutral	None	None	None	None	N
S/T	0.0673	likely_benign	0.0661	benign	-0.227	Destabilizing	0.079	N	0.161	neutral	N	0.400764276	None	None	N
S/V	0.1711	likely_benign	0.1594	benign	-0.212	Destabilizing	0.91	D	0.497	neutral	None	None	None	None	N
S/W	0.363	ambiguous	0.3017	benign	-1.069	Destabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
S/Y	0.1968	likely_benign	0.1685	benign	-0.743	Destabilizing	0.997	D	0.641	neutral	N	0.521805187	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.