TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16913	50962;50963;50964	chr2:178611492;178611491;178611490	chr2:179476219;179476218;179476217
N2AB	15272	46039;46040;46041	chr2:178611492;178611491;178611490	chr2:179476219;179476218;179476217
N2A	14345	43258;43259;43260	chr2:178611492;178611491;178611490	chr2:179476219;179476218;179476217
N2B	7848	23767;23768;23769	chr2:178611492;178611491;178611490	chr2:179476219;179476218;179476217
Novex-1	7973	24142;24143;24144	chr2:178611492;178611491;178611490	chr2:179476219;179476218;179476217
Novex-2	8040	24343;24344;24345	chr2:178611492;178611491;178611490	chr2:179476219;179476218;179476217
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-11
• Domain position: 62
• Structural Position: 92
• Q(SASA): 0.4454
• 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/N	rs559219228	-0.926	0.98	N	0.506	0.221	0.221734844693	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
K/N	rs559219228	-0.926	0.98	N	0.506	0.221	0.221734844693	gnomAD-4.0.0	1.59292E-06	None	None	None	None	N	None	0	2.28833E-05	None	0	0	None	0	0	0	0	0
K/Q	None	None	0.489	N	0.404	0.156	0.246215685461	gnomAD-4.0.0	1.59296E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86144E-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
K/A	0.4475	ambiguous	0.5953	pathogenic	-0.559	Destabilizing	0.97	D	0.567	neutral	None	None	None	None	N
K/C	0.6677	likely_pathogenic	0.8165	pathogenic	-0.556	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
K/D	0.7489	likely_pathogenic	0.8651	pathogenic	-0.235	Destabilizing	0.97	D	0.581	neutral	None	None	None	None	N
K/E	0.3103	likely_benign	0.4403	ambiguous	-0.108	Destabilizing	0.835	D	0.526	neutral	N	0.463313483	None	None	N
K/F	0.8213	likely_pathogenic	0.9011	pathogenic	-0.131	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
K/G	0.6849	likely_pathogenic	0.828	pathogenic	-0.936	Destabilizing	0.985	D	0.613	neutral	None	None	None	None	N
K/H	0.3314	likely_benign	0.423	ambiguous	-1.187	Destabilizing	0.996	D	0.655	neutral	None	None	None	None	N
K/I	0.3348	likely_benign	0.4421	ambiguous	0.423	Stabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
K/L	0.3698	ambiguous	0.4925	ambiguous	0.423	Stabilizing	0.97	D	0.613	neutral	None	None	None	None	N
K/M	0.2647	likely_benign	0.3534	ambiguous	0.151	Stabilizing	0.998	D	0.655	neutral	N	0.481849883	None	None	N
K/N	0.5592	ambiguous	0.6926	pathogenic	-0.596	Destabilizing	0.98	D	0.506	neutral	N	0.4729407	None	None	N
K/P	0.7897	likely_pathogenic	0.8778	pathogenic	0.126	Stabilizing	0.999	D	0.643	neutral	None	None	None	None	N
K/Q	0.1744	likely_benign	0.2156	benign	-0.578	Destabilizing	0.489	N	0.404	neutral	N	0.477085407	None	None	N
K/R	0.0816	likely_benign	0.0927	benign	-0.686	Destabilizing	0.031	N	0.18	neutral	N	0.412535183	None	None	N
K/S	0.5376	ambiguous	0.6775	pathogenic	-1.166	Destabilizing	0.97	D	0.51	neutral	None	None	None	None	N
K/T	0.1881	likely_benign	0.2566	benign	-0.831	Destabilizing	0.98	D	0.565	neutral	N	0.418320239	None	None	N
K/V	0.2971	likely_benign	0.411	ambiguous	0.126	Stabilizing	0.996	D	0.673	neutral	None	None	None	None	N
K/W	0.7943	likely_pathogenic	0.8788	pathogenic	-0.06	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
K/Y	0.6925	likely_pathogenic	0.8205	pathogenic	0.203	Stabilizing	0.999	D	0.723	prob.delet.	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.