TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30094	90505;90506;90507	chr2:178552620;178552619;178552618	chr2:179417347;179417346;179417345
N2AB	28453	85582;85583;85584	chr2:178552620;178552619;178552618	chr2:179417347;179417346;179417345
N2A	27526	82801;82802;82803	chr2:178552620;178552619;178552618	chr2:179417347;179417346;179417345
N2B	21029	63310;63311;63312	chr2:178552620;178552619;178552618	chr2:179417347;179417346;179417345
Novex-1	21154	63685;63686;63687	chr2:178552620;178552619;178552618	chr2:179417347;179417346;179417345
Novex-2	21221	63886;63887;63888	chr2:178552620;178552619;178552618	chr2:179417347;179417346;179417345
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: Fn3-107
• Domain position: 65
• Structural Position: 98
• Q(SASA): 0.8221
• 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	0.967	N	0.582	0.315	0.394079506076	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	0.3827	ambiguous	0.316	benign	-0.014	Destabilizing	0.916	D	0.535	neutral	None	None	None	None	N
K/C	0.7589	likely_pathogenic	0.7004	pathogenic	-0.345	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
K/D	0.6249	likely_pathogenic	0.5454	ambiguous	0.074	Stabilizing	0.987	D	0.637	neutral	None	None	None	None	N
K/E	0.2083	likely_benign	0.1669	benign	0.103	Stabilizing	0.892	D	0.501	neutral	N	0.497431526	None	None	N
K/F	0.8305	likely_pathogenic	0.7796	pathogenic	-0.143	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
K/G	0.5232	ambiguous	0.4433	ambiguous	-0.232	Destabilizing	0.975	D	0.497	neutral	None	None	None	None	N
K/H	0.3395	likely_benign	0.2941	benign	-0.401	Destabilizing	0.997	D	0.651	neutral	None	None	None	None	N
K/I	0.4085	ambiguous	0.3394	benign	0.487	Stabilizing	0.987	D	0.681	prob.neutral	None	None	None	None	N
K/L	0.4307	ambiguous	0.3531	ambiguous	0.487	Stabilizing	0.975	D	0.497	neutral	None	None	None	None	N
K/M	0.2983	likely_benign	0.2461	benign	0.122	Stabilizing	0.999	D	0.643	neutral	N	0.477057232	None	None	N
K/N	0.4965	ambiguous	0.4157	ambiguous	0.053	Stabilizing	0.967	D	0.63	neutral	N	0.515942716	None	None	N
K/P	0.6557	likely_pathogenic	0.5944	pathogenic	0.349	Stabilizing	0.996	D	0.649	neutral	None	None	None	None	N
K/Q	0.1424	likely_benign	0.1232	benign	-0.052	Destabilizing	0.967	D	0.629	neutral	N	0.502512059	None	None	N
K/R	0.0825	likely_benign	0.0773	benign	-0.088	Destabilizing	0.025	N	0.205	neutral	N	0.451640521	None	None	N
K/S	0.4757	ambiguous	0.3985	ambiguous	-0.427	Destabilizing	0.916	D	0.571	neutral	None	None	None	None	N
K/T	0.2104	likely_benign	0.1702	benign	-0.24	Destabilizing	0.967	D	0.582	neutral	N	0.480789992	None	None	N
K/V	0.3876	ambiguous	0.3195	benign	0.349	Stabilizing	0.987	D	0.631	neutral	None	None	None	None	N
K/W	0.7702	likely_pathogenic	0.7162	pathogenic	-0.176	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
K/Y	0.7066	likely_pathogenic	0.6415	pathogenic	0.172	Stabilizing	0.996	D	0.652	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.