TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31803	95632;95633;95634	chr2:178545829;178545828;178545827	chr2:179410556;179410555;179410554
N2AB	30162	90709;90710;90711	chr2:178545829;178545828;178545827	chr2:179410556;179410555;179410554
N2A	29235	87928;87929;87930	chr2:178545829;178545828;178545827	chr2:179410556;179410555;179410554
N2B	22738	68437;68438;68439	chr2:178545829;178545828;178545827	chr2:179410556;179410555;179410554
Novex-1	22863	68812;68813;68814	chr2:178545829;178545828;178545827	chr2:179410556;179410555;179410554
Novex-2	22930	69013;69014;69015	chr2:178545829;178545828;178545827	chr2:179410556;179410555;179410554
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-119
• Domain position: 96
• Structural Position: 132
• Q(SASA): 0.9119
• 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
N/T	rs2154145420	None	0.997	N	0.711	0.336	0.349429436713	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	3.16456E-03	0	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
N/A	0.693	likely_pathogenic	0.6798	pathogenic	-0.239	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
N/C	0.7132	likely_pathogenic	0.686	pathogenic	0.351	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
N/D	0.1709	likely_benign	0.1754	benign	0.086	Stabilizing	0.997	D	0.631	neutral	N	0.453958468	None	None	N
N/E	0.7937	likely_pathogenic	0.792	pathogenic	0.031	Stabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
N/F	0.8741	likely_pathogenic	0.8647	pathogenic	-0.704	Destabilizing	1.0	D	0.729	deleterious	None	None	None	None	N
N/G	0.7332	likely_pathogenic	0.7113	pathogenic	-0.375	Destabilizing	0.998	D	0.522	neutral	None	None	None	None	N
N/H	0.3681	ambiguous	0.3398	benign	-0.431	Destabilizing	0.999	D	0.777	deleterious	N	0.455363978	None	None	N
N/I	0.5831	likely_pathogenic	0.5786	pathogenic	0.027	Stabilizing	0.999	D	0.741	deleterious	N	0.481409915	None	None	N
N/K	0.8808	likely_pathogenic	0.8814	pathogenic	0.144	Stabilizing	0.999	D	0.729	deleterious	N	0.507483522	None	None	N
N/L	0.5999	likely_pathogenic	0.586	pathogenic	0.027	Stabilizing	0.999	D	0.668	prob.neutral	None	None	None	None	N
N/M	0.7066	likely_pathogenic	0.6975	pathogenic	0.343	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
N/P	0.7785	likely_pathogenic	0.7879	pathogenic	-0.036	Destabilizing	0.999	D	0.721	deleterious	None	None	None	None	N
N/Q	0.7992	likely_pathogenic	0.7925	pathogenic	-0.278	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	N
N/R	0.8981	likely_pathogenic	0.8955	pathogenic	0.213	Stabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
N/S	0.2065	likely_benign	0.202	benign	-0.02	Destabilizing	0.997	D	0.529	neutral	N	0.488455044	None	None	N
N/T	0.4565	ambiguous	0.439	ambiguous	0.054	Stabilizing	0.997	D	0.711	prob.delet.	N	0.456457269	None	None	N
N/V	0.6227	likely_pathogenic	0.6134	pathogenic	-0.036	Destabilizing	0.999	D	0.679	prob.neutral	None	None	None	None	N
N/W	0.9575	likely_pathogenic	0.9545	pathogenic	-0.735	Destabilizing	1.0	D	0.727	deleterious	None	None	None	None	N
N/Y	0.4694	ambiguous	0.456	ambiguous	-0.45	Destabilizing	1.0	D	0.75	deleterious	N	0.480665067	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.