TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30072	90439;90440;90441	chr2:178552686;178552685;178552684	chr2:179417413;179417412;179417411
N2AB	28431	85516;85517;85518	chr2:178552686;178552685;178552684	chr2:179417413;179417412;179417411
N2A	27504	82735;82736;82737	chr2:178552686;178552685;178552684	chr2:179417413;179417412;179417411
N2B	21007	63244;63245;63246	chr2:178552686;178552685;178552684	chr2:179417413;179417412;179417411
Novex-1	21132	63619;63620;63621	chr2:178552686;178552685;178552684	chr2:179417413;179417412;179417411
Novex-2	21199	63820;63821;63822	chr2:178552686;178552685;178552684	chr2:179417413;179417412;179417411
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: Fn3-107
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.7767
• 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/R	None	None	0.029	N	0.341	0.106	0.31411915649	gnomAD-4.0.0	1.59105E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85781E-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	0.2154	likely_benign	0.1856	benign	0.004	Stabilizing	0.016	N	0.39	neutral	None	None	None	None	N
K/C	0.6029	likely_pathogenic	0.5607	ambiguous	-0.497	Destabilizing	0.864	D	0.439	neutral	None	None	None	None	N
K/D	0.4172	ambiguous	0.3587	ambiguous	-0.191	Destabilizing	0.016	N	0.439	neutral	None	None	None	None	N
K/E	0.1327	likely_benign	0.1143	benign	-0.202	Destabilizing	None	N	0.163	neutral	N	0.504608214	None	None	N
K/F	0.5921	likely_pathogenic	0.5639	ambiguous	-0.348	Destabilizing	0.214	N	0.473	neutral	None	None	None	None	N
K/G	0.3895	ambiguous	0.3238	benign	-0.122	Destabilizing	0.016	N	0.469	neutral	None	None	None	None	N
K/H	0.2785	likely_benign	0.2479	benign	-0.225	Destabilizing	0.001	N	0.287	neutral	None	None	None	None	N
K/I	0.1834	likely_benign	0.1713	benign	0.249	Stabilizing	None	N	0.383	neutral	N	0.517577512	None	None	N
K/L	0.2543	likely_benign	0.2219	benign	0.249	Stabilizing	0.006	N	0.483	neutral	None	None	None	None	N
K/M	0.1735	likely_benign	0.1541	benign	-0.085	Destabilizing	0.214	N	0.435	neutral	None	None	None	None	N
K/N	0.2885	likely_benign	0.2477	benign	-0.028	Destabilizing	0.055	N	0.316	neutral	N	0.504629644	None	None	N
K/P	0.424	ambiguous	0.3621	ambiguous	0.191	Stabilizing	0.136	N	0.459	neutral	None	None	None	None	N
K/Q	0.1097	likely_benign	0.1001	benign	-0.161	Destabilizing	None	N	0.18	neutral	N	0.503589494	None	None	N
K/R	0.0812	likely_benign	0.0791	benign	-0.111	Destabilizing	0.029	N	0.341	neutral	N	0.472814043	None	None	N
K/S	0.2798	likely_benign	0.2411	benign	-0.415	Destabilizing	None	N	0.156	neutral	None	None	None	None	N
K/T	0.1404	likely_benign	0.1212	benign	-0.306	Destabilizing	0.029	N	0.421	neutral	N	0.485118377	None	None	N
K/V	0.1993	likely_benign	0.1799	benign	0.191	Stabilizing	0.006	N	0.472	neutral	None	None	None	None	N
K/W	0.7005	likely_pathogenic	0.6707	pathogenic	-0.444	Destabilizing	0.864	D	0.449	neutral	None	None	None	None	N
K/Y	0.5201	ambiguous	0.4864	ambiguous	-0.085	Destabilizing	0.214	N	0.485	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.