TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35438	106537;106538;106539	chr2:178530303;178530302;178530301	chr2:179395030;179395029;179395028
N2AB	33797	101614;101615;101616	chr2:178530303;178530302;178530301	chr2:179395030;179395029;179395028
N2A	32870	98833;98834;98835	chr2:178530303;178530302;178530301	chr2:179395030;179395029;179395028
N2B	26373	79342;79343;79344	chr2:178530303;178530302;178530301	chr2:179395030;179395029;179395028
Novex-1	26498	79717;79718;79719	chr2:178530303;178530302;178530301	chr2:179395030;179395029;179395028
Novex-2	26565	79918;79919;79920	chr2:178530303;178530302;178530301	chr2:179395030;179395029;179395028
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: Ig-166
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.4048
• 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	rs755067124	0.401	0.076	N	0.684	0.243	0.144782658237	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	1.29166E-04	0	None	0	0	None	0	None	0	0	0
K/E	rs755067124	0.401	0.076	N	0.684	0.243	0.144782658237	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
K/E	rs755067124	0.401	0.076	N	0.684	0.243	0.144782658237	gnomAD-4.0.0	3.09871E-06	None	None	None	None	N	None	4.00427E-05	0	None	0	2.22787E-05	None	0	0	8.47709E-07	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	0.3573	ambiguous	0.3601	ambiguous	-0.416	Destabilizing	0.345	N	0.661	neutral	None	None	None	None	N
K/C	0.7948	likely_pathogenic	0.7916	pathogenic	-0.512	Destabilizing	0.977	D	0.729	prob.delet.	None	None	None	None	N
K/D	0.6865	likely_pathogenic	0.6919	pathogenic	-0.083	Destabilizing	0.209	N	0.621	neutral	None	None	None	None	N
K/E	0.223	likely_benign	0.2187	benign	0.038	Stabilizing	0.076	N	0.684	prob.neutral	N	0.443393892	None	None	N
K/F	0.7725	likely_pathogenic	0.7667	pathogenic	-0.062	Destabilizing	0.919	D	0.725	prob.delet.	None	None	None	None	N
K/G	0.5198	ambiguous	0.5285	ambiguous	-0.765	Destabilizing	0.209	N	0.647	neutral	None	None	None	None	N
K/H	0.3756	ambiguous	0.3776	ambiguous	-0.892	Destabilizing	0.649	D	0.685	prob.neutral	None	None	None	None	N
K/I	0.3136	likely_benign	0.3053	benign	0.482	Stabilizing	0.739	D	0.722	prob.delet.	N	0.450666581	None	None	N
K/L	0.3693	ambiguous	0.372	ambiguous	0.482	Stabilizing	0.345	N	0.626	neutral	None	None	None	None	N
K/M	0.2632	likely_benign	0.2637	benign	0.068	Stabilizing	0.977	D	0.678	prob.neutral	None	None	None	None	N
K/N	0.4083	ambiguous	0.4126	ambiguous	-0.388	Destabilizing	0.001	N	0.471	neutral	N	0.467964263	None	None	N
K/P	0.9022	likely_pathogenic	0.9153	pathogenic	0.212	Stabilizing	0.789	D	0.67	neutral	None	None	None	None	N
K/Q	0.1654	likely_benign	0.1633	benign	-0.36	Destabilizing	0.005	N	0.497	neutral	N	0.454765679	None	None	N
K/R	0.0943	likely_benign	0.0938	benign	-0.432	Destabilizing	0.166	N	0.668	neutral	N	0.432176821	None	None	N
K/S	0.3831	ambiguous	0.3928	ambiguous	-0.943	Destabilizing	0.209	N	0.662	neutral	None	None	None	None	N
K/T	0.1501	likely_benign	0.1493	benign	-0.618	Destabilizing	0.166	N	0.61	neutral	N	0.417089938	None	None	N
K/V	0.2901	likely_benign	0.2883	benign	0.212	Stabilizing	0.789	D	0.665	neutral	None	None	None	None	N
K/W	0.8312	likely_pathogenic	0.832	pathogenic	-0.022	Destabilizing	0.977	D	0.721	prob.delet.	None	None	None	None	N
K/Y	0.6517	likely_pathogenic	0.6475	pathogenic	0.257	Stabilizing	0.919	D	0.701	prob.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.