TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23735	71428;71429;71430	chr2:178574929;178574928;178574927	chr2:179439656;179439655;179439654
N2AB	22094	66505;66506;66507	chr2:178574929;178574928;178574927	chr2:179439656;179439655;179439654
N2A	21167	63724;63725;63726	chr2:178574929;178574928;178574927	chr2:179439656;179439655;179439654
N2B	14670	44233;44234;44235	chr2:178574929;178574928;178574927	chr2:179439656;179439655;179439654
Novex-1	14795	44608;44609;44610	chr2:178574929;178574928;178574927	chr2:179439656;179439655;179439654
Novex-2	14862	44809;44810;44811	chr2:178574929;178574928;178574927	chr2:179439656;179439655;179439654
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: Fn3-60
• Domain position: 10
• Structural Position: 11
• Q(SASA): 0.5121
• 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/R	None	None	0.001	N	0.36	0.16	0.227934060464	gnomAD-4.0.0	1.59311E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02792E-05

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	0.3121	likely_benign	0.3198	benign	-0.481	Destabilizing	0.272	N	0.617	neutral	None	None	None	None	N
K/C	0.4315	ambiguous	0.4406	ambiguous	-0.521	Destabilizing	0.968	D	0.793	deleterious	None	None	None	None	N
K/D	0.6084	likely_pathogenic	0.5885	pathogenic	0.144	Stabilizing	0.157	N	0.659	neutral	None	None	None	None	N
K/E	0.2105	likely_benign	0.2139	benign	0.229	Stabilizing	0.124	N	0.575	neutral	N	0.457875847	None	None	N
K/F	0.6685	likely_pathogenic	0.6505	pathogenic	-0.331	Destabilizing	0.726	D	0.767	deleterious	None	None	None	None	N
K/G	0.515	ambiguous	0.5059	ambiguous	-0.804	Destabilizing	0.157	N	0.628	neutral	None	None	None	None	N
K/H	0.1689	likely_benign	0.1745	benign	-1.12	Destabilizing	0.726	D	0.715	prob.delet.	None	None	None	None	N
K/I	0.2107	likely_benign	0.2049	benign	0.33	Stabilizing	0.667	D	0.772	deleterious	N	0.49339393	None	None	N
K/L	0.2742	likely_benign	0.272	benign	0.33	Stabilizing	0.567	D	0.649	neutral	None	None	None	None	N
K/M	0.2035	likely_benign	0.1987	benign	0.181	Stabilizing	0.968	D	0.69	prob.neutral	None	None	None	None	N
K/N	0.3699	ambiguous	0.356	ambiguous	-0.268	Destabilizing	0.001	N	0.251	neutral	N	0.509208745	None	None	N
K/P	0.94	likely_pathogenic	0.902	pathogenic	0.09	Stabilizing	0.726	D	0.726	prob.delet.	None	None	None	None	N
K/Q	0.1038	likely_benign	0.1118	benign	-0.355	Destabilizing	0.331	N	0.593	neutral	N	0.446138701	None	None	N
K/R	0.0727	likely_benign	0.0746	benign	-0.449	Destabilizing	0.001	N	0.36	neutral	N	0.435729706	None	None	N
K/S	0.3542	ambiguous	0.3594	ambiguous	-0.934	Destabilizing	0.157	N	0.565	neutral	None	None	None	None	N
K/T	0.1271	likely_benign	0.137	benign	-0.648	Destabilizing	0.22	N	0.659	neutral	N	0.44994701	None	None	N
K/V	0.1957	likely_benign	0.1984	benign	0.09	Stabilizing	0.567	D	0.725	prob.delet.	None	None	None	None	N
K/W	0.6986	likely_pathogenic	0.6616	pathogenic	-0.214	Destabilizing	0.968	D	0.759	deleterious	None	None	None	None	N
K/Y	0.5059	ambiguous	0.4775	ambiguous	0.084	Stabilizing	0.726	D	0.759	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.