TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22502	67729;67730;67731	chr2:178579693;178579692;178579691	chr2:179444420;179444419;179444418
N2AB	20861	62806;62807;62808	chr2:178579693;178579692;178579691	chr2:179444420;179444419;179444418
N2A	19934	60025;60026;60027	chr2:178579693;178579692;178579691	chr2:179444420;179444419;179444418
N2B	13437	40534;40535;40536	chr2:178579693;178579692;178579691	chr2:179444420;179444419;179444418
Novex-1	13562	40909;40910;40911	chr2:178579693;178579692;178579691	chr2:179444420;179444419;179444418
Novex-2	13629	41110;41111;41112	chr2:178579693;178579692;178579691	chr2:179444420;179444419;179444418
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: Fn3-51
• Domain position: 52
• Structural Position: 70
• Q(SASA): 0.6616
• 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/N	None	None	0.722	N	0.582	0.123	0.0920862733494	gnomAD-4.0.0	1.59224E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86015E-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	0.3471	ambiguous	0.4904	ambiguous	-0.148	Destabilizing	0.775	D	0.643	neutral	None	None	None	None	N
K/C	0.574	likely_pathogenic	0.6876	pathogenic	-0.379	Destabilizing	0.996	D	0.765	deleterious	None	None	None	None	N
K/D	0.5229	ambiguous	0.686	pathogenic	0.241	Stabilizing	0.923	D	0.647	neutral	None	None	None	None	N
K/E	0.1979	likely_benign	0.2844	benign	0.27	Stabilizing	0.722	D	0.576	neutral	N	0.426166073	None	None	N
K/F	0.6912	likely_pathogenic	0.8428	pathogenic	-0.227	Destabilizing	0.987	D	0.733	prob.delet.	None	None	None	None	N
K/G	0.4282	ambiguous	0.5985	pathogenic	-0.388	Destabilizing	0.775	D	0.638	neutral	None	None	None	None	N
K/H	0.2255	likely_benign	0.2998	benign	-0.629	Destabilizing	0.961	D	0.674	neutral	None	None	None	None	N
K/I	0.3334	likely_benign	0.4774	ambiguous	0.413	Stabilizing	0.949	D	0.734	prob.delet.	N	0.500565045	None	None	N
K/L	0.3391	likely_benign	0.4995	ambiguous	0.413	Stabilizing	0.775	D	0.638	neutral	None	None	None	None	N
K/M	0.2503	likely_benign	0.3696	ambiguous	0.216	Stabilizing	0.996	D	0.665	neutral	None	None	None	None	N
K/N	0.3284	likely_benign	0.5015	ambiguous	0.107	Stabilizing	0.722	D	0.582	neutral	N	0.470879643	None	None	N
K/P	0.706	likely_pathogenic	0.8201	pathogenic	0.255	Stabilizing	0.961	D	0.675	prob.neutral	None	None	None	None	N
K/Q	0.1315	likely_benign	0.1709	benign	-0.073	Destabilizing	0.722	D	0.599	neutral	N	0.490601554	None	None	N
K/R	0.0761	likely_benign	0.0873	benign	-0.105	Destabilizing	0.003	N	0.161	neutral	N	0.440538093	None	None	N
K/S	0.3411	ambiguous	0.5183	ambiguous	-0.501	Destabilizing	0.775	D	0.549	neutral	None	None	None	None	N
K/T	0.154	likely_benign	0.2211	benign	-0.304	Destabilizing	0.722	D	0.645	neutral	N	0.451581806	None	None	N
K/V	0.2961	likely_benign	0.4033	ambiguous	0.255	Stabilizing	0.923	D	0.647	neutral	None	None	None	None	N
K/W	0.6507	likely_pathogenic	0.7992	pathogenic	-0.154	Destabilizing	0.996	D	0.775	deleterious	None	None	None	None	N
K/Y	0.4969	ambiguous	0.6643	pathogenic	0.179	Stabilizing	0.987	D	0.734	prob.delet.	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.