TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3850	11773;11774;11775	chr2:178741685;178741684;178741683	chr2:179606412;179606411;179606410
N2AB	3533	10822;10823;10824	chr2:178741685;178741684;178741683	chr2:179606412;179606411;179606410
N2A	None	None	chr2:None	chr2:None
N2B	3487	10684;10685;10686	chr2:178741685;178741684;178741683	chr2:179606412;179606411;179606410
Novex-1	3612	11059;11060;11061	chr2:178741685;178741684;178741683	chr2:179606412;179606411;179606410
Novex-2	3679	11260;11261;11262	chr2:178741685;178741684;178741683	chr2:179606412;179606411;179606410
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-27
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.8237
• Predicted PPI site: I

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
K/E	None	None	0.012	N	0.442	0.075	None	gnomAD-4.0.0	1.59128E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8584E-06	0	0
K/R	rs763263943	0.004	None	N	0.25	0.08	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/R	rs763263943	0.004	None	N	0.25	0.08	None	gnomAD-4.0.0	1.59128E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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
K/A	0.2707	likely_benign	0.2848	benign	-0.062	Destabilizing	0.016	N	0.325	neutral	None	None	None	None	I
K/C	0.6809	likely_pathogenic	0.7212	pathogenic	-0.211	Destabilizing	0.864	D	0.423	neutral	None	None	None	None	I
K/D	0.4166	ambiguous	0.4171	ambiguous	0.106	Stabilizing	0.072	N	0.495	neutral	None	None	None	None	I
K/E	0.1008	likely_benign	0.0976	benign	0.135	Stabilizing	0.012	N	0.442	neutral	N	0.456904444	None	None	I
K/F	0.7136	likely_pathogenic	0.7061	pathogenic	-0.127	Destabilizing	0.214	N	0.453	neutral	None	None	None	None	I
K/G	0.4112	ambiguous	0.4323	ambiguous	-0.306	Destabilizing	0.072	N	0.485	neutral	None	None	None	None	I
K/H	0.2959	likely_benign	0.3101	benign	-0.609	Destabilizing	0.214	N	0.487	neutral	None	None	None	None	I
K/I	0.2614	likely_benign	0.2489	benign	0.513	Stabilizing	0.001	N	0.297	neutral	N	0.508425192	None	None	I
K/L	0.3145	likely_benign	0.3215	benign	0.513	Stabilizing	0.016	N	0.331	neutral	None	None	None	None	I
K/M	0.1953	likely_benign	0.191	benign	0.257	Stabilizing	0.356	N	0.489	neutral	None	None	None	None	I
K/N	0.2615	likely_benign	0.258	benign	0.149	Stabilizing	0.055	N	0.45	neutral	N	0.501537122	None	None	I
K/P	0.7803	likely_pathogenic	0.8388	pathogenic	0.351	Stabilizing	0.136	N	0.562	neutral	None	None	None	None	I
K/Q	0.1077	likely_benign	0.113	benign	0.006	Stabilizing	None	N	0.164	neutral	N	0.496674728	None	None	I
K/R	0.0834	likely_benign	0.0867	benign	-0.154	Destabilizing	None	N	0.25	neutral	N	0.503373505	None	None	I
K/S	0.304	likely_benign	0.2988	benign	-0.364	Destabilizing	0.016	N	0.423	neutral	None	None	None	None	I
K/T	0.1411	likely_benign	0.1388	benign	-0.171	Destabilizing	None	N	0.199	neutral	N	0.47886906	None	None	I
K/V	0.2537	likely_benign	0.2485	benign	0.351	Stabilizing	0.001	N	0.269	neutral	None	None	None	None	I
K/W	0.7534	likely_pathogenic	0.7719	pathogenic	-0.114	Destabilizing	0.864	D	0.434	neutral	None	None	None	None	I
K/Y	0.5648	likely_pathogenic	0.5711	pathogenic	0.218	Stabilizing	0.356	N	0.474	neutral	None	None	None	None	I

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.