TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21946	66061;66062;66063	chr2:178582967;178582966;178582965	chr2:179447694;179447693;179447692
N2AB	20305	61138;61139;61140	chr2:178582967;178582966;178582965	chr2:179447694;179447693;179447692
N2A	19378	58357;58358;58359	chr2:178582967;178582966;178582965	chr2:179447694;179447693;179447692
N2B	12881	38866;38867;38868	chr2:178582967;178582966;178582965	chr2:179447694;179447693;179447692
Novex-1	13006	39241;39242;39243	chr2:178582967;178582966;178582965	chr2:179447694;179447693;179447692
Novex-2	13073	39442;39443;39444	chr2:178582967;178582966;178582965	chr2:179447694;179447693;179447692
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: Ig-125
• Domain position: 81
• Structural Position: 168
• Q(SASA): 0.4465
• 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/P	None	None	0.873	N	0.571	0.424	0.347879110917	gnomAD-4.0.0	1.76504E-06	None	None	None	None	N	None	0	0	None	0	2.87555E-05	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
S/A	0.082	likely_benign	0.0848	benign	-0.299	Destabilizing	0.166	N	0.336	neutral	N	0.519687602	None	None	N
S/C	0.1332	likely_benign	0.1126	benign	-0.236	Destabilizing	0.991	D	0.507	neutral	None	None	None	None	N
S/D	0.4305	ambiguous	0.428	ambiguous	0.038	Stabilizing	0.39	N	0.385	neutral	None	None	None	None	N
S/E	0.413	ambiguous	0.4185	ambiguous	-0.074	Destabilizing	0.017	N	0.177	neutral	None	None	None	None	N
S/F	0.1872	likely_benign	0.1644	benign	-0.997	Destabilizing	0.004	N	0.425	neutral	None	None	None	None	N
S/G	0.1357	likely_benign	0.1359	benign	-0.365	Destabilizing	0.345	N	0.388	neutral	None	None	None	None	N
S/H	0.3408	ambiguous	0.2864	benign	-0.901	Destabilizing	0.818	D	0.527	neutral	None	None	None	None	N
S/I	0.166	likely_benign	0.1617	benign	-0.257	Destabilizing	0.561	D	0.555	neutral	None	None	None	None	N
S/K	0.5892	likely_pathogenic	0.5599	ambiguous	-0.397	Destabilizing	0.004	N	0.188	neutral	None	None	None	None	N
S/L	0.1123	likely_benign	0.1066	benign	-0.257	Destabilizing	0.166	N	0.452	neutral	D	0.537620002	None	None	N
S/M	0.1494	likely_benign	0.1429	benign	0.029	Stabilizing	0.965	D	0.523	neutral	None	None	None	None	N
S/N	0.1436	likely_benign	0.1382	benign	-0.109	Destabilizing	0.561	D	0.377	neutral	None	None	None	None	N
S/P	0.7837	likely_pathogenic	0.7788	pathogenic	-0.245	Destabilizing	0.873	D	0.571	neutral	N	0.498204859	None	None	N
S/Q	0.4157	ambiguous	0.3798	ambiguous	-0.402	Destabilizing	0.561	D	0.429	neutral	None	None	None	None	N
S/R	0.5711	likely_pathogenic	0.5445	ambiguous	-0.186	Destabilizing	0.39	N	0.518	neutral	None	None	None	None	N
S/T	0.0636	likely_benign	0.0659	benign	-0.224	Destabilizing	0.013	N	0.151	neutral	N	0.449227439	None	None	N
S/V	0.159	likely_benign	0.1541	benign	-0.245	Destabilizing	0.39	N	0.502	neutral	None	None	None	None	N
S/W	0.394	ambiguous	0.3314	benign	-1.019	Destabilizing	0.991	D	0.53	neutral	None	None	None	None	N
S/Y	0.186	likely_benign	0.1532	benign	-0.729	Destabilizing	0.007	N	0.332	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.