TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22852	68779;68780;68781	chr2:178577872;178577871;178577870	chr2:179442599;179442598;179442597
N2AB	21211	63856;63857;63858	chr2:178577872;178577871;178577870	chr2:179442599;179442598;179442597
N2A	20284	61075;61076;61077	chr2:178577872;178577871;178577870	chr2:179442599;179442598;179442597
N2B	13787	41584;41585;41586	chr2:178577872;178577871;178577870	chr2:179442599;179442598;179442597
Novex-1	13912	41959;41960;41961	chr2:178577872;178577871;178577870	chr2:179442599;179442598;179442597
Novex-2	13979	42160;42161;42162	chr2:178577872;178577871;178577870	chr2:179442599;179442598;179442597
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: Fn3-54
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.6548
• 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/K	rs780727295	0.604	0.124	N	0.586	0.105	0.0954503805726	gnomAD-2.1.1	1.74E-05	None	None	None	None	N	None	0	0	None	0	2.30229E-04	None	0	None	0	0	0
N/K	rs780727295	0.604	0.124	N	0.586	0.105	0.0954503805726	gnomAD-4.0.0	3.3017E-06	None	None	None	None	N	None	0	0	None	0	5.60538E-05	None	0	0	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	0.1942	likely_benign	0.176	benign	-0.557	Destabilizing	0.157	N	0.569	neutral	None	None	None	None	N
N/C	0.2511	likely_benign	0.2296	benign	0.208	Stabilizing	0.909	D	0.663	neutral	None	None	None	None	N
N/D	0.1304	likely_benign	0.1172	benign	0.009	Stabilizing	0.001	N	0.227	neutral	N	0.393016292	None	None	N
N/E	0.4246	ambiguous	0.3791	ambiguous	0.016	Stabilizing	0.157	N	0.591	neutral	None	None	None	None	N
N/F	0.5302	ambiguous	0.4999	ambiguous	-0.688	Destabilizing	0.726	D	0.665	neutral	None	None	None	None	N
N/G	0.2203	likely_benign	0.2083	benign	-0.796	Destabilizing	0.072	N	0.617	neutral	None	None	None	None	N
N/H	0.1137	likely_benign	0.1084	benign	-0.725	Destabilizing	0.667	D	0.574	neutral	D	0.524735557	None	None	N
N/I	0.3071	likely_benign	0.2489	benign	None	Stabilizing	0.497	N	0.654	neutral	N	0.486563958	None	None	N
N/K	0.4578	ambiguous	0.42	ambiguous	-0.033	Destabilizing	0.124	N	0.586	neutral	N	0.480675349	None	None	N
N/L	0.2561	likely_benign	0.2352	benign	None	Stabilizing	0.567	D	0.569	neutral	None	None	None	None	N
N/M	0.315	likely_benign	0.2895	benign	0.385	Stabilizing	0.968	D	0.628	neutral	None	None	None	None	N
N/P	0.9276	likely_pathogenic	0.9121	pathogenic	-0.157	Destabilizing	0.567	D	0.621	neutral	None	None	None	None	N
N/Q	0.3417	ambiguous	0.3217	benign	-0.579	Destabilizing	0.567	D	0.558	neutral	None	None	None	None	N
N/R	0.424	ambiguous	0.4189	ambiguous	-0.003	Destabilizing	0.567	D	0.553	neutral	None	None	None	None	N
N/S	0.057	likely_benign	0.0542	benign	-0.423	Destabilizing	0.001	N	0.11	neutral	N	0.458009133	None	None	N
N/T	0.104	likely_benign	0.0969	benign	-0.248	Destabilizing	0.124	N	0.574	neutral	N	0.492892498	None	None	N
N/V	0.293	likely_benign	0.2442	benign	-0.157	Destabilizing	0.567	D	0.637	neutral	None	None	None	None	N
N/W	0.7533	likely_pathogenic	0.7376	pathogenic	-0.551	Destabilizing	0.968	D	0.723	prob.delet.	None	None	None	None	N
N/Y	0.2013	likely_benign	0.1818	benign	-0.328	Destabilizing	0.667	D	0.639	neutral	N	0.47192867	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.