TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33406	100441;100442;100443	chr2:178536531;178536530;178536529	chr2:179401258;179401257;179401256
N2AB	31765	95518;95519;95520	chr2:178536531;178536530;178536529	chr2:179401258;179401257;179401256
N2A	30838	92737;92738;92739	chr2:178536531;178536530;178536529	chr2:179401258;179401257;179401256
N2B	24341	73246;73247;73248	chr2:178536531;178536530;178536529	chr2:179401258;179401257;179401256
Novex-1	24466	73621;73622;73623	chr2:178536531;178536530;178536529	chr2:179401258;179401257;179401256
Novex-2	24533	73822;73823;73824	chr2:178536531;178536530;178536529	chr2:179401258;179401257;179401256
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: Fn3-131
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.436
• 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
K/T	None	None	0.896	N	0.542	0.238	0.326616659874	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.3984	ambiguous	0.4021	ambiguous	-0.23	Destabilizing	0.034	N	0.332	neutral	None	None	None	None	N
K/C	0.8824	likely_pathogenic	0.8609	pathogenic	-0.312	Destabilizing	0.997	D	0.707	prob.neutral	None	None	None	None	N
K/D	0.7718	likely_pathogenic	0.8022	pathogenic	-0.07	Destabilizing	0.976	D	0.517	neutral	None	None	None	None	N
K/E	0.2717	likely_benign	0.299	benign	-0.067	Destabilizing	0.811	D	0.509	neutral	N	0.481248565	None	None	N
K/F	0.9433	likely_pathogenic	0.9495	pathogenic	-0.565	Destabilizing	0.988	D	0.701	prob.neutral	None	None	None	None	N
K/G	0.5238	ambiguous	0.5288	ambiguous	-0.443	Destabilizing	0.851	D	0.562	neutral	None	None	None	None	N
K/H	0.6327	likely_pathogenic	0.6138	pathogenic	-0.91	Destabilizing	0.997	D	0.543	neutral	None	None	None	None	N
K/I	0.6485	likely_pathogenic	0.6812	pathogenic	0.255	Stabilizing	0.968	D	0.699	prob.neutral	N	0.482991806	None	None	N
K/L	0.6569	likely_pathogenic	0.6816	pathogenic	0.255	Stabilizing	0.919	D	0.553	neutral	None	None	None	None	N
K/M	0.4581	ambiguous	0.4754	ambiguous	0.396	Stabilizing	0.999	D	0.541	neutral	None	None	None	None	N
K/N	0.601	likely_pathogenic	0.6438	pathogenic	0.14	Stabilizing	0.984	D	0.504	neutral	N	0.491966991	None	None	N
K/P	0.7459	likely_pathogenic	0.7818	pathogenic	0.121	Stabilizing	0.988	D	0.573	neutral	None	None	None	None	N
K/Q	0.2362	likely_benign	0.2239	benign	-0.188	Destabilizing	0.437	N	0.261	neutral	N	0.516633362	None	None	N
K/R	0.1091	likely_benign	0.1027	benign	-0.018	Destabilizing	0.896	D	0.475	neutral	N	0.449832367	None	None	N
K/S	0.5087	ambiguous	0.5281	ambiguous	-0.449	Destabilizing	0.851	D	0.495	neutral	None	None	None	None	N
K/T	0.3232	likely_benign	0.3482	ambiguous	-0.295	Destabilizing	0.896	D	0.542	neutral	N	0.515246496	None	None	N
K/V	0.5793	likely_pathogenic	0.5917	pathogenic	0.121	Stabilizing	0.952	D	0.548	neutral	None	None	None	None	N
K/W	0.9405	likely_pathogenic	0.9443	pathogenic	-0.474	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
K/Y	0.8862	likely_pathogenic	0.8958	pathogenic	-0.088	Destabilizing	0.996	D	0.67	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.