TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14504	43735;43736;43737	chr2:178632384;178632383;178632382	chr2:179497111;179497110;179497109
N2AB	12863	38812;38813;38814	chr2:178632384;178632383;178632382	chr2:179497111;179497110;179497109
N2A	11936	36031;36032;36033	chr2:178632384;178632383;178632382	chr2:179497111;179497110;179497109
N2B	5439	16540;16541;16542	chr2:178632384;178632383;178632382	chr2:179497111;179497110;179497109
Novex-1	5564	16915;16916;16917	chr2:178632384;178632383;178632382	chr2:179497111;179497110;179497109
Novex-2	5631	17116;17117;17118	chr2:178632384;178632383;178632382	chr2:179497111;179497110;179497109
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: Ig-96
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.7709
• 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	0.001	N	0.247	0.145	0.255270683199	gnomAD-4.0.0	6.91768E-07	None	None	None	None	N	None	3.02499E-05	0	None	0	0	None	0	0	0	0	0
K/R	None	None	0.22	D	0.545	0.182	0.238096912614	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.3017	likely_benign	0.2627	benign	-0.12	Destabilizing	0.157	N	0.532	neutral	None	None	None	None	N
K/C	0.7713	likely_pathogenic	0.7527	pathogenic	-0.323	Destabilizing	0.909	D	0.663	neutral	None	None	None	None	N
K/D	0.5247	ambiguous	0.4604	ambiguous	-0.05	Destabilizing	0.157	N	0.565	neutral	None	None	None	None	N
K/E	0.1148	likely_benign	0.0985	benign	0.012	Stabilizing	0.001	N	0.247	neutral	N	0.509397105	None	None	N
K/F	0.813	likely_pathogenic	0.7751	pathogenic	-0.047	Destabilizing	0.726	D	0.651	neutral	None	None	None	None	N
K/G	0.4402	ambiguous	0.3909	ambiguous	-0.394	Destabilizing	0.272	N	0.513	neutral	None	None	None	None	N
K/H	0.3621	ambiguous	0.3038	benign	-0.641	Destabilizing	0.909	D	0.607	neutral	None	None	None	None	N
K/I	0.3836	ambiguous	0.356	ambiguous	0.551	Stabilizing	0.331	N	0.658	neutral	D	0.588564077	None	None	N
K/L	0.39	ambiguous	0.3494	ambiguous	0.551	Stabilizing	0.157	N	0.513	neutral	None	None	None	None	N
K/M	0.2508	likely_benign	0.2419	benign	0.11	Stabilizing	0.909	D	0.61	neutral	None	None	None	None	N
K/N	0.3533	ambiguous	0.2949	benign	-0.068	Destabilizing	0.497	N	0.557	neutral	D	0.562328336	None	None	N
K/P	0.7532	likely_pathogenic	0.7039	pathogenic	0.357	Stabilizing	0.726	D	0.619	neutral	None	None	None	None	N
K/Q	0.1331	likely_benign	0.1144	benign	-0.122	Destabilizing	0.331	N	0.583	neutral	N	0.497327958	None	None	N
K/R	0.0954	likely_benign	0.0916	benign	-0.271	Destabilizing	0.22	N	0.545	neutral	D	0.557523696	None	None	N
K/S	0.3582	ambiguous	0.296	benign	-0.517	Destabilizing	0.157	N	0.534	neutral	None	None	None	None	N
K/T	0.1248	likely_benign	0.1145	benign	-0.283	Destabilizing	0.001	N	0.313	neutral	D	0.561429223	None	None	N
K/V	0.3403	ambiguous	0.3081	benign	0.357	Stabilizing	0.396	N	0.523	neutral	None	None	None	None	N
K/W	0.8259	likely_pathogenic	0.8028	pathogenic	-0.067	Destabilizing	0.968	D	0.678	prob.neutral	None	None	None	None	N
K/Y	0.6913	likely_pathogenic	0.6446	pathogenic	0.249	Stabilizing	0.726	D	0.643	neutral	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.