TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21059	63400;63401;63402	chr2:178588550;178588549;178588548	chr2:179453277;179453276;179453275
N2AB	19418	58477;58478;58479	chr2:178588550;178588549;178588548	chr2:179453277;179453276;179453275
N2A	18491	55696;55697;55698	chr2:178588550;178588549;178588548	chr2:179453277;179453276;179453275
N2B	11994	36205;36206;36207	chr2:178588550;178588549;178588548	chr2:179453277;179453276;179453275
Novex-1	12119	36580;36581;36582	chr2:178588550;178588549;178588548	chr2:179453277;179453276;179453275
Novex-2	12186	36781;36782;36783	chr2:178588550;178588549;178588548	chr2:179453277;179453276;179453275
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-40
• Domain position: 97
• Structural Position: 131
• Q(SASA): 0.4359
• 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
K/E	None	None	0.997	N	0.648	0.275	0.285698343383	gnomAD-4.0.0	1.45525E-06	None	None	None	None	N	None	3.2817E-05	0	None	0	0	None	0	0	9.31982E-07	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
K/A	0.5739	likely_pathogenic	0.4356	ambiguous	-0.393	Destabilizing	0.998	D	0.702	prob.delet.	None	None	None	None	N
K/C	0.7145	likely_pathogenic	0.5861	pathogenic	-0.39	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
K/D	0.9028	likely_pathogenic	0.8291	pathogenic	-0.164	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
K/E	0.3962	ambiguous	0.2989	benign	-0.089	Destabilizing	0.997	D	0.648	neutral	N	0.466102967	None	None	N
K/F	0.9033	likely_pathogenic	0.8343	pathogenic	-0.207	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/G	0.6715	likely_pathogenic	0.5343	ambiguous	-0.729	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
K/H	0.4588	ambiguous	0.3672	ambiguous	-1.17	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
K/I	0.6352	likely_pathogenic	0.5046	ambiguous	0.458	Stabilizing	0.999	D	0.809	deleterious	N	0.46897202	None	None	N
K/L	0.6307	likely_pathogenic	0.5022	ambiguous	0.458	Stabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
K/M	0.4383	ambiguous	0.3158	benign	0.376	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	N
K/N	0.7801	likely_pathogenic	0.66	pathogenic	-0.313	Destabilizing	0.999	D	0.659	prob.neutral	N	0.483126256	None	None	N
K/P	0.982	likely_pathogenic	0.9687	pathogenic	0.205	Stabilizing	0.999	D	0.707	prob.delet.	None	None	None	None	N
K/Q	0.2133	likely_benign	0.1622	benign	-0.436	Destabilizing	0.999	D	0.691	prob.delet.	N	0.485595592	None	None	N
K/R	0.0777	likely_benign	0.0754	benign	-0.595	Destabilizing	0.997	D	0.618	neutral	N	0.463489524	None	None	N
K/S	0.6845	likely_pathogenic	0.5497	ambiguous	-0.893	Destabilizing	0.998	D	0.703	prob.delet.	None	None	None	None	N
K/T	0.3861	ambiguous	0.2726	benign	-0.629	Destabilizing	0.999	D	0.705	prob.delet.	N	0.491214843	None	None	N
K/V	0.5218	ambiguous	0.4058	ambiguous	0.205	Stabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
K/W	0.8566	likely_pathogenic	0.7799	pathogenic	-0.115	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/Y	0.8427	likely_pathogenic	0.7402	pathogenic	0.182	Stabilizing	1.0	D	0.791	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.