TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29740	89443;89444;89445	chr2:178553787;178553786;178553785	chr2:179418514;179418513;179418512
N2AB	28099	84520;84521;84522	chr2:178553787;178553786;178553785	chr2:179418514;179418513;179418512
N2A	27172	81739;81740;81741	chr2:178553787;178553786;178553785	chr2:179418514;179418513;179418512
N2B	20675	62248;62249;62250	chr2:178553787;178553786;178553785	chr2:179418514;179418513;179418512
Novex-1	20800	62623;62624;62625	chr2:178553787;178553786;178553785	chr2:179418514;179418513;179418512
Novex-2	20867	62824;62825;62826	chr2:178553787;178553786;178553785	chr2:179418514;179418513;179418512
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: Fn3-105
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.5526
• 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	0.999	N	0.635	0.268	0.31501682445	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	0.4072	ambiguous	0.3715	ambiguous	0.031	Stabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
K/C	0.7517	likely_pathogenic	0.7439	pathogenic	-0.308	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/D	0.6257	likely_pathogenic	0.5669	pathogenic	0.075	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
K/E	0.3417	ambiguous	0.2742	benign	0.081	Stabilizing	0.999	D	0.635	neutral	N	0.50175991	None	None	N
K/F	0.8446	likely_pathogenic	0.8338	pathogenic	-0.187	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
K/G	0.4867	ambiguous	0.4631	ambiguous	-0.158	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
K/H	0.371	ambiguous	0.3622	ambiguous	-0.351	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
K/I	0.4846	ambiguous	0.4651	ambiguous	0.447	Stabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
K/L	0.5311	ambiguous	0.4991	ambiguous	0.447	Stabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
K/M	0.3571	ambiguous	0.3324	benign	0.174	Stabilizing	1.0	D	0.693	prob.neutral	N	0.481421644	None	None	N
K/N	0.4605	ambiguous	0.4251	ambiguous	0.149	Stabilizing	1.0	D	0.728	prob.delet.	N	0.463158663	None	None	N
K/P	0.8037	likely_pathogenic	0.7683	pathogenic	0.336	Stabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
K/Q	0.2088	likely_benign	0.1867	benign	-0.011	Destabilizing	1.0	D	0.706	prob.neutral	N	0.490985556	None	None	N
K/R	0.0976	likely_benign	0.0954	benign	-0.021	Destabilizing	0.999	D	0.596	neutral	N	0.480923278	None	None	N
K/S	0.4952	ambiguous	0.4491	ambiguous	-0.336	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
K/T	0.2714	likely_benign	0.2391	benign	-0.183	Destabilizing	1.0	D	0.774	deleterious	N	0.495180655	None	None	N
K/V	0.3803	ambiguous	0.3649	ambiguous	0.336	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
K/W	0.8539	likely_pathogenic	0.8464	pathogenic	-0.213	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
K/Y	0.6837	likely_pathogenic	0.6751	pathogenic	0.144	Stabilizing	1.0	D	0.775	deleterious	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.