TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2378	7357;7358;7359	chr2:178774036;178774035;178774034	chr2:179638763;179638762;179638761
N2AB	2378	7357;7358;7359	chr2:178774036;178774035;178774034	chr2:179638763;179638762;179638761
N2A	2378	7357;7358;7359	chr2:178774036;178774035;178774034	chr2:179638763;179638762;179638761
N2B	2332	7219;7220;7221	chr2:178774036;178774035;178774034	chr2:179638763;179638762;179638761
Novex-1	2332	7219;7220;7221	chr2:178774036;178774035;178774034	chr2:179638763;179638762;179638761
Novex-2	2332	7219;7220;7221	chr2:178774036;178774035;178774034	chr2:179638763;179638762;179638761
Novex-3	2378	7357;7358;7359	chr2:178774036;178774035;178774034	chr2:179638763;179638762;179638761

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-13
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.39
• 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	rs727503690	-0.483	0.031	N	0.203	0.281	0.235038932564	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/R	rs727503690	-0.483	0.031	N	0.203	0.281	0.235038932564	gnomAD-4.0.0	6.36256E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.73099E-05	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	0.8309	likely_pathogenic	0.8216	pathogenic	-0.751	Destabilizing	0.97	D	0.643	neutral	None	None	None	None	N
K/C	0.9256	likely_pathogenic	0.9136	pathogenic	-1.076	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
K/D	0.952	likely_pathogenic	0.9535	pathogenic	-0.86	Destabilizing	0.996	D	0.693	prob.neutral	None	None	None	None	N
K/E	0.6866	likely_pathogenic	0.6691	pathogenic	-0.707	Destabilizing	0.961	D	0.565	neutral	N	0.458068216	None	None	N
K/F	0.9702	likely_pathogenic	0.969	pathogenic	-0.302	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
K/G	0.9198	likely_pathogenic	0.9225	pathogenic	-1.148	Destabilizing	0.985	D	0.681	prob.neutral	None	None	None	None	N
K/H	0.6334	likely_pathogenic	0.6204	pathogenic	-1.469	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
K/I	0.7678	likely_pathogenic	0.7647	pathogenic	0.303	Stabilizing	0.998	D	0.723	prob.delet.	N	0.516994154	None	None	N
K/L	0.7472	likely_pathogenic	0.7341	pathogenic	0.303	Stabilizing	0.97	D	0.681	prob.neutral	None	None	None	None	N
K/M	0.5898	likely_pathogenic	0.5604	ambiguous	0.069	Stabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
K/N	0.8619	likely_pathogenic	0.8582	pathogenic	-1.1	Destabilizing	0.98	D	0.573	neutral	N	0.506569646	None	None	N
K/P	0.9858	likely_pathogenic	0.988	pathogenic	-0.02	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
K/Q	0.3619	ambiguous	0.3409	ambiguous	-1.1	Destabilizing	0.961	D	0.587	neutral	N	0.511086878	None	None	N
K/R	0.113	likely_benign	0.1149	benign	-0.974	Destabilizing	0.031	N	0.203	neutral	N	0.46400864	None	None	N
K/S	0.8744	likely_pathogenic	0.8662	pathogenic	-1.673	Destabilizing	0.985	D	0.534	neutral	None	None	None	None	N
K/T	0.5706	likely_pathogenic	0.5504	ambiguous	-1.311	Destabilizing	0.98	D	0.65	neutral	N	0.501412316	None	None	N
K/V	0.7259	likely_pathogenic	0.7188	pathogenic	-0.02	Destabilizing	0.996	D	0.689	prob.neutral	None	None	None	None	N
K/W	0.9583	likely_pathogenic	0.9549	pathogenic	-0.25	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
K/Y	0.9327	likely_pathogenic	0.9297	pathogenic	0.083	Stabilizing	0.999	D	0.731	prob.delet.	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.