TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14362	43309;43310;43311	chr2:178633189;178633188;178633187	chr2:179497916;179497915;179497914
N2AB	12721	38386;38387;38388	chr2:178633189;178633188;178633187	chr2:179497916;179497915;179497914
N2A	11794	35605;35606;35607	chr2:178633189;178633188;178633187	chr2:179497916;179497915;179497914
N2B	5297	16114;16115;16116	chr2:178633189;178633188;178633187	chr2:179497916;179497915;179497914
Novex-1	5422	16489;16490;16491	chr2:178633189;178633188;178633187	chr2:179497916;179497915;179497914
Novex-2	5489	16690;16691;16692	chr2:178633189;178633188;178633187	chr2:179497916;179497915;179497914
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-94
• Domain position: 44
• Structural Position: 111
• Q(SASA): 0.6583
• 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
P/L	None	None	0.993	N	0.563	0.384	0.458917189328	gnomAD-4.0.0	1.59968E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87579E-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
P/A	0.0882	likely_benign	0.0766	benign	-0.169	Destabilizing	0.355	N	0.378	neutral	N	0.434062786	None	None	N
P/C	0.6729	likely_pathogenic	0.6095	pathogenic	-0.527	Destabilizing	1.0	D	0.7	prob.delet.	None	None	None	None	N
P/D	0.3808	ambiguous	0.3012	benign	-0.318	Destabilizing	0.995	D	0.594	neutral	None	None	None	None	N
P/E	0.2425	likely_benign	0.2	benign	-0.452	Destabilizing	0.995	D	0.585	neutral	None	None	None	None	N
P/F	0.6589	likely_pathogenic	0.5723	pathogenic	-0.644	Destabilizing	1.0	D	0.642	neutral	None	None	None	None	N
P/G	0.3807	ambiguous	0.3074	benign	-0.226	Destabilizing	0.982	D	0.452	neutral	None	None	None	None	N
P/H	0.2232	likely_benign	0.1992	benign	0.09	Stabilizing	1.0	D	0.544	neutral	N	0.503370876	None	None	N
P/I	0.4101	ambiguous	0.3461	ambiguous	-0.174	Destabilizing	0.997	D	0.701	prob.delet.	None	None	None	None	N
P/K	0.236	likely_benign	0.1927	benign	-0.203	Destabilizing	0.995	D	0.579	neutral	None	None	None	None	N
P/L	0.1633	likely_benign	0.141	benign	-0.174	Destabilizing	0.993	D	0.563	neutral	N	0.505307563	None	None	N
P/M	0.4082	ambiguous	0.3413	ambiguous	-0.319	Destabilizing	1.0	D	0.547	neutral	None	None	None	None	N
P/N	0.3676	ambiguous	0.2939	benign	0.082	Stabilizing	0.995	D	0.631	neutral	None	None	None	None	N
P/Q	0.1719	likely_benign	0.1445	benign	-0.174	Destabilizing	0.997	D	0.485	neutral	None	None	None	None	N
P/R	0.1636	likely_benign	0.1442	benign	0.262	Stabilizing	0.997	D	0.593	neutral	N	0.483677505	None	None	N
P/S	0.1337	likely_benign	0.1108	benign	-0.199	Destabilizing	0.787	D	0.365	neutral	N	0.412387068	None	None	N
P/T	0.1175	likely_benign	0.0996	benign	-0.244	Destabilizing	0.976	D	0.622	neutral	D	0.523350325	None	None	N
P/V	0.289	likely_benign	0.2469	benign	-0.142	Destabilizing	0.995	D	0.457	neutral	None	None	None	None	N
P/W	0.7631	likely_pathogenic	0.6849	pathogenic	-0.721	Destabilizing	1.0	D	0.737	deleterious	None	None	None	None	N
P/Y	0.5958	likely_pathogenic	0.5128	ambiguous	-0.41	Destabilizing	1.0	D	0.641	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.