TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30438	91537;91538;91539	chr2:178551219;178551218;178551217	chr2:179415946;179415945;179415944
N2AB	28797	86614;86615;86616	chr2:178551219;178551218;178551217	chr2:179415946;179415945;179415944
N2A	27870	83833;83834;83835	chr2:178551219;178551218;178551217	chr2:179415946;179415945;179415944
N2B	21373	64342;64343;64344	chr2:178551219;178551218;178551217	chr2:179415946;179415945;179415944
Novex-1	21498	64717;64718;64719	chr2:178551219;178551218;178551217	chr2:179415946;179415945;179415944
Novex-2	21565	64918;64919;64920	chr2:178551219;178551218;178551217	chr2:179415946;179415945;179415944
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-110
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1626
• 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
T/A	None	None	0.835	N	0.387	0.143	0.215869574891	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	3.66327E-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
T/A	0.1535	likely_benign	0.1583	benign	-0.818	Destabilizing	0.835	D	0.387	neutral	N	0.463436382	None	None	N
T/C	0.5153	ambiguous	0.4907	ambiguous	-0.928	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
T/D	0.6593	likely_pathogenic	0.698	pathogenic	-1.583	Destabilizing	0.97	D	0.641	neutral	None	None	None	None	N
T/E	0.5574	ambiguous	0.5847	pathogenic	-1.521	Destabilizing	0.97	D	0.629	neutral	None	None	None	None	N
T/F	0.4858	ambiguous	0.479	ambiguous	-0.962	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
T/G	0.3367	likely_benign	0.3692	ambiguous	-1.093	Destabilizing	0.97	D	0.581	neutral	None	None	None	None	N
T/H	0.3928	ambiguous	0.4008	ambiguous	-1.416	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
T/I	0.646	likely_pathogenic	0.6326	pathogenic	-0.159	Destabilizing	0.994	D	0.697	prob.neutral	N	0.492439235	None	None	N
T/K	0.4822	ambiguous	0.5056	ambiguous	-0.716	Destabilizing	0.97	D	0.637	neutral	None	None	None	None	N
T/L	0.3082	likely_benign	0.3058	benign	-0.159	Destabilizing	0.985	D	0.57	neutral	None	None	None	None	N
T/M	0.1261	likely_benign	0.1228	benign	0.067	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
T/N	0.1631	likely_benign	0.1731	benign	-1.084	Destabilizing	0.961	D	0.519	neutral	N	0.516308075	None	None	N
T/P	0.9652	likely_pathogenic	0.9663	pathogenic	-0.348	Destabilizing	0.994	D	0.699	prob.neutral	N	0.503795541	None	None	N
T/Q	0.3725	ambiguous	0.376	ambiguous	-1.271	Destabilizing	0.996	D	0.716	prob.delet.	None	None	None	None	N
T/R	0.4497	ambiguous	0.4808	ambiguous	-0.522	Destabilizing	0.996	D	0.699	prob.neutral	None	None	None	None	N
T/S	0.1053	likely_benign	0.1076	benign	-1.189	Destabilizing	0.287	N	0.213	neutral	N	0.36501604	None	None	N
T/V	0.4328	ambiguous	0.4172	ambiguous	-0.348	Destabilizing	0.985	D	0.478	neutral	None	None	None	None	N
T/W	0.8255	likely_pathogenic	0.8247	pathogenic	-1.009	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
T/Y	0.4568	ambiguous	0.4604	ambiguous	-0.647	Destabilizing	0.999	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.