TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8840	26743;26744;26745	chr2:178714140;178714139;178714138	chr2:179578867;179578866;179578865
N2AB	8523	25792;25793;25794	chr2:178714140;178714139;178714138	chr2:179578867;179578866;179578865
N2A	7596	23011;23012;23013	chr2:178714140;178714139;178714138	chr2:179578867;179578866;179578865
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-74
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.6391
• 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/Q	None	None	0.001	N	0.195	0.108	0.0482279557977	gnomAD-4.0.0	1.59287E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86056E-06	0	0
K/T	rs2077106214	None	None	N	0.103	0.118	0.0716867268079	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/T	rs2077106214	None	None	N	0.103	0.118	0.0716867268079	gnomAD-4.0.0	6.57013E-06	None	None	None	None	N	None	2.41185E-05	0	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
K/A	0.1401	likely_benign	0.1507	benign	-0.072	Destabilizing	0.007	N	0.185	neutral	None	None	None	None	N
K/C	0.4218	ambiguous	0.5107	ambiguous	-0.439	Destabilizing	0.356	N	0.317	neutral	None	None	None	None	N
K/D	0.2677	likely_benign	0.2957	benign	0.093	Stabilizing	None	N	0.122	neutral	None	None	None	None	N
K/E	0.0975	likely_benign	0.0997	benign	0.105	Stabilizing	0.005	N	0.197	neutral	N	0.428564165	None	None	N
K/F	0.4044	ambiguous	0.47	ambiguous	-0.291	Destabilizing	0.356	N	0.383	neutral	None	None	None	None	N
K/G	0.2399	likely_benign	0.2792	benign	-0.261	Destabilizing	0.016	N	0.261	neutral	None	None	None	None	N
K/H	0.1493	likely_benign	0.1776	benign	-0.461	Destabilizing	0.214	N	0.327	neutral	None	None	None	None	N
K/I	0.1446	likely_benign	0.1648	benign	0.344	Stabilizing	0.029	N	0.482	neutral	N	0.452694606	None	None	N
K/L	0.1413	likely_benign	0.1724	benign	0.344	Stabilizing	0.016	N	0.313	neutral	None	None	None	None	N
K/M	0.1005	likely_benign	0.1091	benign	0.049	Stabilizing	0.356	N	0.33	neutral	None	None	None	None	N
K/N	0.1515	likely_benign	0.1787	benign	0.022	Stabilizing	None	N	0.125	neutral	N	0.438879947	None	None	N
K/P	0.4535	ambiguous	0.4901	ambiguous	0.233	Stabilizing	0.072	N	0.422	neutral	None	None	None	None	N
K/Q	0.0861	likely_benign	0.0912	benign	-0.117	Destabilizing	0.001	N	0.195	neutral	N	0.429201671	None	None	N
K/R	0.068	likely_benign	0.0744	benign	-0.11	Destabilizing	None	N	0.095	neutral	N	0.461602091	None	None	N
K/S	0.1434	likely_benign	0.1611	benign	-0.471	Destabilizing	None	N	0.092	neutral	None	None	None	None	N
K/T	0.0611	likely_benign	0.0604	benign	-0.308	Destabilizing	None	N	0.103	neutral	N	0.394126305	None	None	N
K/V	0.1405	likely_benign	0.1584	benign	0.233	Stabilizing	0.016	N	0.353	neutral	None	None	None	None	N
K/W	0.4251	ambiguous	0.5272	ambiguous	-0.308	Destabilizing	0.864	D	0.327	neutral	None	None	None	None	N
K/Y	0.2918	likely_benign	0.3716	ambiguous	0.045	Stabilizing	0.356	N	0.399	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.