TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23689	71290;71291;71292	chr2:178575067;178575066;178575065	chr2:179439794;179439793;179439792
N2AB	22048	66367;66368;66369	chr2:178575067;178575066;178575065	chr2:179439794;179439793;179439792
N2A	21121	63586;63587;63588	chr2:178575067;178575066;178575065	chr2:179439794;179439793;179439792
N2B	14624	44095;44096;44097	chr2:178575067;178575066;178575065	chr2:179439794;179439793;179439792
Novex-1	14749	44470;44471;44472	chr2:178575067;178575066;178575065	chr2:179439794;179439793;179439792
Novex-2	14816	44671;44672;44673	chr2:178575067;178575066;178575065	chr2:179439794;179439793;179439792
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: Ig-130
• Domain position: 53
• Structural Position: 136
• Q(SASA): 0.1388
• 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	rs755034022	-1.105	0.726	N	0.621	0.172	0.119812018005	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
T/A	rs755034022	-1.105	0.726	N	0.621	0.172	0.119812018005	gnomAD-4.0.0	3.42185E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49789E-06	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
T/A	0.1064	likely_benign	0.1102	benign	-1.183	Destabilizing	0.726	D	0.621	neutral	N	0.475100879	None	None	N
T/C	0.4623	ambiguous	0.4707	ambiguous	-1.016	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
T/D	0.9268	likely_pathogenic	0.9487	pathogenic	-2.064	Highly Destabilizing	0.983	D	0.764	deleterious	None	None	None	None	N
T/E	0.9302	likely_pathogenic	0.95	pathogenic	-1.779	Destabilizing	0.983	D	0.757	deleterious	None	None	None	None	N
T/F	0.7547	likely_pathogenic	0.7949	pathogenic	-0.8	Destabilizing	0.992	D	0.826	deleterious	None	None	None	None	N
T/G	0.5027	ambiguous	0.5381	ambiguous	-1.651	Destabilizing	0.895	D	0.709	prob.delet.	None	None	None	None	N
T/H	0.8195	likely_pathogenic	0.8683	pathogenic	-1.797	Destabilizing	0.998	D	0.824	deleterious	None	None	None	None	N
T/I	0.4287	ambiguous	0.4542	ambiguous	0.078	Stabilizing	0.989	D	0.799	deleterious	N	0.459464323	None	None	N
T/K	0.9281	likely_pathogenic	0.9516	pathogenic	-0.416	Destabilizing	0.968	D	0.758	deleterious	None	None	None	None	N
T/L	0.2528	likely_benign	0.254	benign	0.078	Stabilizing	0.944	D	0.685	prob.neutral	None	None	None	None	N
T/M	0.1901	likely_benign	0.2114	benign	-0.151	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
T/N	0.5615	ambiguous	0.6233	pathogenic	-1.484	Destabilizing	0.957	D	0.739	prob.delet.	N	0.491726557	None	None	N
T/P	0.9238	likely_pathogenic	0.9319	pathogenic	-0.312	Destabilizing	0.989	D	0.796	deleterious	N	0.460478281	None	None	N
T/Q	0.8369	likely_pathogenic	0.8788	pathogenic	-1.026	Destabilizing	0.983	D	0.801	deleterious	None	None	None	None	N
T/R	0.8927	likely_pathogenic	0.9249	pathogenic	-0.928	Destabilizing	0.983	D	0.797	deleterious	None	None	None	None	N
T/S	0.1759	likely_benign	0.2011	benign	-1.631	Destabilizing	0.146	N	0.487	neutral	N	0.468654909	None	None	N
T/V	0.2186	likely_benign	0.223	benign	-0.312	Destabilizing	0.944	D	0.621	neutral	None	None	None	None	N
T/W	0.9641	likely_pathogenic	0.9729	pathogenic	-1.111	Destabilizing	0.999	D	0.819	deleterious	None	None	None	None	N
T/Y	0.8436	likely_pathogenic	0.8817	pathogenic	-0.651	Destabilizing	0.997	D	0.825	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.