TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15650	47173;47174;47175	chr2:178618602;178618601;178618600	chr2:179483329;179483328;179483327
N2AB	14009	42250;42251;42252	chr2:178618602;178618601;178618600	chr2:179483329;179483328;179483327
N2A	13082	39469;39470;39471	chr2:178618602;178618601;178618600	chr2:179483329;179483328;179483327
N2B	6585	19978;19979;19980	chr2:178618602;178618601;178618600	chr2:179483329;179483328;179483327
Novex-1	6710	20353;20354;20355	chr2:178618602;178618601;178618600	chr2:179483329;179483328;179483327
Novex-2	6777	20554;20555;20556	chr2:178618602;178618601;178618600	chr2:179483329;179483328;179483327
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-108
• Domain position: 83
• Structural Position: 172
• Q(SASA): 0.0694
• 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
I/M	rs1397752957	-1.217	1.0	N	0.717	0.383	0.516106911764	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
I/M	rs1397752957	-1.217	1.0	N	0.717	0.383	0.516106911764	gnomAD-4.0.0	6.84999E-07	None	None	None	None	N	None	0	2.24437E-05	None	0	0	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
I/A	0.7965	likely_pathogenic	0.8667	pathogenic	-2.802	Highly Destabilizing	0.999	D	0.589	neutral	None	None	None	None	N
I/C	0.8	likely_pathogenic	0.8648	pathogenic	-2.199	Highly Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
I/D	0.9928	likely_pathogenic	0.9941	pathogenic	-3.56	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
I/E	0.9735	likely_pathogenic	0.9745	pathogenic	-3.273	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
I/F	0.3184	likely_benign	0.3512	ambiguous	-1.569	Destabilizing	1.0	D	0.688	prob.neutral	N	0.507620127	None	None	N
I/G	0.9587	likely_pathogenic	0.9755	pathogenic	-3.382	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
I/H	0.9375	likely_pathogenic	0.9472	pathogenic	-3.02	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
I/K	0.9276	likely_pathogenic	0.9346	pathogenic	-2.172	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
I/L	0.1683	likely_benign	0.2097	benign	-1.07	Destabilizing	0.993	D	0.393	neutral	N	0.498552089	None	None	N
I/M	0.2052	likely_benign	0.2311	benign	-1.271	Destabilizing	1.0	D	0.717	prob.delet.	N	0.509584452	None	None	N
I/N	0.9003	likely_pathogenic	0.9228	pathogenic	-2.756	Highly Destabilizing	1.0	D	0.855	deleterious	N	0.510982371	None	None	N
I/P	0.988	likely_pathogenic	0.9927	pathogenic	-1.636	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
I/Q	0.9139	likely_pathogenic	0.9174	pathogenic	-2.48	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
I/R	0.8758	likely_pathogenic	0.8893	pathogenic	-2.055	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
I/S	0.8573	likely_pathogenic	0.9059	pathogenic	-3.345	Highly Destabilizing	1.0	D	0.78	deleterious	N	0.508716885	None	None	N
I/T	0.7858	likely_pathogenic	0.8368	pathogenic	-2.91	Highly Destabilizing	1.0	D	0.745	deleterious	N	0.507620127	None	None	N
I/V	0.1117	likely_benign	0.131	benign	-1.636	Destabilizing	0.993	D	0.339	neutral	N	0.498770902	None	None	N
I/W	0.9183	likely_pathogenic	0.9238	pathogenic	-2.073	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
I/Y	0.8304	likely_pathogenic	0.8348	pathogenic	-1.853	Destabilizing	1.0	D	0.804	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.