TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31537	94834;94835;94836	chr2:178546819;178546818;178546817	chr2:179411546;179411545;179411544
N2AB	29896	89911;89912;89913	chr2:178546819;178546818;178546817	chr2:179411546;179411545;179411544
N2A	28969	87130;87131;87132	chr2:178546819;178546818;178546817	chr2:179411546;179411545;179411544
N2B	22472	67639;67640;67641	chr2:178546819;178546818;178546817	chr2:179411546;179411545;179411544
Novex-1	22597	68014;68015;68016	chr2:178546819;178546818;178546817	chr2:179411546;179411545;179411544
Novex-2	22664	68215;68216;68217	chr2:178546819;178546818;178546817	chr2:179411546;179411545;179411544
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-118
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7204
• 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/N	None	None	0.999	N	0.708	0.314	0.256283259241	gnomAD-4.0.0	6.85101E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00709E-07	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
K/A	0.5075	ambiguous	0.4896	ambiguous	-0.027	Destabilizing	0.998	D	0.577	neutral	None	None	None	None	I
K/C	0.8067	likely_pathogenic	0.8063	pathogenic	-0.181	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
K/D	0.8218	likely_pathogenic	0.8293	pathogenic	0.038	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
K/E	0.4132	ambiguous	0.411	ambiguous	0.047	Stabilizing	0.996	D	0.569	neutral	N	0.481152565	None	None	I
K/F	0.9303	likely_pathogenic	0.9308	pathogenic	-0.212	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	I
K/G	0.6909	likely_pathogenic	0.7068	pathogenic	-0.238	Destabilizing	1.0	D	0.579	neutral	None	None	None	None	I
K/H	0.469	ambiguous	0.473	ambiguous	-0.528	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	I
K/I	0.6412	likely_pathogenic	0.6168	pathogenic	0.452	Stabilizing	1.0	D	0.665	neutral	None	None	None	None	I
K/L	0.5801	likely_pathogenic	0.5698	pathogenic	0.452	Stabilizing	1.0	D	0.579	neutral	None	None	None	None	I
K/M	0.469	ambiguous	0.4521	ambiguous	0.275	Stabilizing	1.0	D	0.667	neutral	D	0.524215482	None	None	I
K/N	0.7288	likely_pathogenic	0.7418	pathogenic	0.2	Stabilizing	0.999	D	0.708	prob.delet.	N	0.4725341	None	None	I
K/P	0.5507	ambiguous	0.5049	ambiguous	0.321	Stabilizing	1.0	D	0.675	neutral	None	None	None	None	I
K/Q	0.2211	likely_benign	0.2187	benign	0.02	Stabilizing	0.999	D	0.71	prob.delet.	N	0.468900023	None	None	I
K/R	0.0781	likely_benign	0.0787	benign	-0.06	Destabilizing	0.64	D	0.291	neutral	N	0.461473513	None	None	I
K/S	0.6639	likely_pathogenic	0.67	pathogenic	-0.295	Destabilizing	0.998	D	0.645	neutral	None	None	None	None	I
K/T	0.3896	ambiguous	0.3865	ambiguous	-0.133	Destabilizing	0.999	D	0.639	neutral	N	0.501818625	None	None	I
K/V	0.5102	ambiguous	0.4777	ambiguous	0.321	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	I
K/W	0.901	likely_pathogenic	0.9007	pathogenic	-0.215	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
K/Y	0.8516	likely_pathogenic	0.8573	pathogenic	0.134	Stabilizing	1.0	D	0.681	prob.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.