TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23181	69766;69767;69768	chr2:178576703;178576702;178576701	chr2:179441430;179441429;179441428
N2AB	21540	64843;64844;64845	chr2:178576703;178576702;178576701	chr2:179441430;179441429;179441428
N2A	20613	62062;62063;62064	chr2:178576703;178576702;178576701	chr2:179441430;179441429;179441428
N2B	14116	42571;42572;42573	chr2:178576703;178576702;178576701	chr2:179441430;179441429;179441428
Novex-1	14241	42946;42947;42948	chr2:178576703;178576702;178576701	chr2:179441430;179441429;179441428
Novex-2	14308	43147;43148;43149	chr2:178576703;178576702;178576701	chr2:179441430;179441429;179441428
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: Fn3-56
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.6501
• 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/E	None	None	0.822	N	0.555	0.24	0.282575091529	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.4206	ambiguous	0.4293	ambiguous	-0.263	Destabilizing	0.754	D	0.577	neutral	None	None	None	None	N
K/C	0.7843	likely_pathogenic	0.7834	pathogenic	-0.356	Destabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	N
K/D	0.7414	likely_pathogenic	0.7617	pathogenic	0.11	Stabilizing	0.956	D	0.552	neutral	None	None	None	None	N
K/E	0.2549	likely_benign	0.2663	benign	0.146	Stabilizing	0.822	D	0.555	neutral	N	0.50568565	None	None	N
K/F	0.8688	likely_pathogenic	0.8632	pathogenic	-0.291	Destabilizing	0.978	D	0.679	prob.neutral	None	None	None	None	N
K/G	0.4683	ambiguous	0.4866	ambiguous	-0.532	Destabilizing	0.86	D	0.589	neutral	None	None	None	None	N
K/H	0.4451	ambiguous	0.4493	ambiguous	-0.878	Destabilizing	0.998	D	0.581	neutral	None	None	None	None	N
K/I	0.4476	ambiguous	0.4384	ambiguous	0.385	Stabilizing	0.956	D	0.681	prob.neutral	None	None	None	None	N
K/L	0.4429	ambiguous	0.443	ambiguous	0.385	Stabilizing	0.754	D	0.609	neutral	None	None	None	None	N
K/M	0.2853	likely_benign	0.2941	benign	0.316	Stabilizing	0.997	D	0.584	neutral	N	0.479815482	None	None	N
K/N	0.5725	likely_pathogenic	0.5993	pathogenic	0.021	Stabilizing	0.942	D	0.494	neutral	N	0.469535587	None	None	N
K/P	0.7941	likely_pathogenic	0.7865	pathogenic	0.199	Stabilizing	0.978	D	0.585	neutral	None	None	None	None	N
K/Q	0.1508	likely_benign	0.1569	benign	-0.192	Destabilizing	0.942	D	0.538	neutral	N	0.469825075	None	None	N
K/R	0.0856	likely_benign	0.0831	benign	-0.233	Destabilizing	0.014	N	0.249	neutral	N	0.483811655	None	None	N
K/S	0.5329	ambiguous	0.5541	ambiguous	-0.607	Destabilizing	0.754	D	0.525	neutral	None	None	None	None	N
K/T	0.2582	likely_benign	0.2759	benign	-0.398	Destabilizing	0.032	N	0.339	neutral	N	0.507205802	None	None	N
K/V	0.4102	ambiguous	0.4016	ambiguous	0.199	Stabilizing	0.915	D	0.575	neutral	None	None	None	None	N
K/W	0.8348	likely_pathogenic	0.825	pathogenic	-0.182	Destabilizing	0.998	D	0.716	prob.delet.	None	None	None	None	N
K/Y	0.7534	likely_pathogenic	0.7498	pathogenic	0.14	Stabilizing	0.993	D	0.666	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.