TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1563	4912;4913;4914	chr2:178777276;178777275;178777274	chr2:179642003;179642002;179642001
N2AB	1563	4912;4913;4914	chr2:178777276;178777275;178777274	chr2:179642003;179642002;179642001
N2A	1563	4912;4913;4914	chr2:178777276;178777275;178777274	chr2:179642003;179642002;179642001
N2B	1517	4774;4775;4776	chr2:178777276;178777275;178777274	chr2:179642003;179642002;179642001
Novex-1	1517	4774;4775;4776	chr2:178777276;178777275;178777274	chr2:179642003;179642002;179642001
Novex-2	1517	4774;4775;4776	chr2:178777276;178777275;178777274	chr2:179642003;179642002;179642001
Novex-3	1563	4912;4913;4914	chr2:178777276;178777275;178777274	chr2:179642003;179642002;179642001

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-7
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.686
• 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	None	None	0.638	N	0.637	0.164	0.337621943819	gnomAD-4.0.0	1.59083E-06	None	None	None	None	N	None	0	0	None	0	2.77562E-05	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	0.4403	ambiguous	0.4316	ambiguous	0.072	Stabilizing	0.399	N	0.567	neutral	None	None	None	None	N
K/C	0.7067	likely_pathogenic	0.6633	pathogenic	-0.283	Destabilizing	0.982	D	0.647	neutral	None	None	None	None	N
K/D	0.7376	likely_pathogenic	0.7341	pathogenic	-0.223	Destabilizing	0.7	D	0.638	neutral	None	None	None	None	N
K/E	0.2524	likely_benign	0.261	benign	-0.224	Destabilizing	0.201	N	0.548	neutral	N	0.507987155	None	None	N
K/F	0.8493	likely_pathogenic	0.8336	pathogenic	-0.193	Destabilizing	0.947	D	0.614	neutral	None	None	None	None	N
K/G	0.4477	ambiguous	0.4418	ambiguous	-0.088	Destabilizing	0.7	D	0.489	neutral	None	None	None	None	N
K/H	0.3229	likely_benign	0.3032	benign	-0.229	Destabilizing	0.947	D	0.633	neutral	None	None	None	None	N
K/I	0.5102	ambiguous	0.503	ambiguous	0.414	Stabilizing	0.781	D	0.635	neutral	D	0.590121061	None	None	N
K/L	0.4504	ambiguous	0.4392	ambiguous	0.414	Stabilizing	0.7	D	0.489	neutral	None	None	None	None	N
K/M	0.3657	ambiguous	0.3591	ambiguous	0.011	Stabilizing	0.982	D	0.629	neutral	None	None	None	None	N
K/N	0.5387	ambiguous	0.5208	ambiguous	0.16	Stabilizing	0.638	D	0.637	neutral	N	0.515408872	None	None	N
K/P	0.7586	likely_pathogenic	0.7558	pathogenic	0.325	Stabilizing	0.826	D	0.647	neutral	None	None	None	None	N
K/Q	0.128	likely_benign	0.1264	benign	0.018	Stabilizing	0.638	D	0.639	neutral	N	0.469568649	None	None	N
K/R	0.0693	likely_benign	0.069	benign	-0.02	Destabilizing	0.002	N	0.219	neutral	N	0.468380363	None	None	N
K/S	0.496	ambiguous	0.4836	ambiguous	-0.204	Destabilizing	0.399	N	0.601	neutral	None	None	None	None	N
K/T	0.2681	likely_benign	0.265	benign	-0.079	Destabilizing	0.638	D	0.597	neutral	N	0.49482485	None	None	N
K/V	0.4493	ambiguous	0.449	ambiguous	0.325	Stabilizing	0.7	D	0.573	neutral	None	None	None	None	N
K/W	0.7224	likely_pathogenic	0.6966	pathogenic	-0.288	Destabilizing	0.982	D	0.663	neutral	None	None	None	None	N
K/Y	0.7264	likely_pathogenic	0.7033	pathogenic	0.065	Stabilizing	0.826	D	0.581	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.