TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15337	46234;46235;46236	chr2:178620512;178620511;178620510	chr2:179485239;179485238;179485237
N2AB	13696	41311;41312;41313	chr2:178620512;178620511;178620510	chr2:179485239;179485238;179485237
N2A	12769	38530;38531;38532	chr2:178620512;178620511;178620510	chr2:179485239;179485238;179485237
N2B	6272	19039;19040;19041	chr2:178620512;178620511;178620510	chr2:179485239;179485238;179485237
Novex-1	6397	19414;19415;19416	chr2:178620512;178620511;178620510	chr2:179485239;179485238;179485237
Novex-2	6464	19615;19616;19617	chr2:178620512;178620511;178620510	chr2:179485239;179485238;179485237
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-105
• Domain position: 36
• Structural Position: 51
• Q(SASA): 0.609
• 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
N/H	None	None	0.996	D	0.41	0.322	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
N/I	rs762315032	0.101	0.988	D	0.462	0.34	0.528461186488	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14758E-04	0	None	0	0	None	0	None	0	0	0
N/I	rs762315032	0.101	0.988	D	0.462	0.34	0.528461186488	gnomAD-4.0.0	1.71198E-05	None	None	None	None	N	None	2.99473E-05	0	None	0	0	None	0	0	2.16011E-05	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
N/A	0.5144	ambiguous	0.4618	ambiguous	-0.671	Destabilizing	0.079	N	0.185	neutral	None	None	None	None	N
N/C	0.5674	likely_pathogenic	0.5859	pathogenic	0.193	Stabilizing	0.999	D	0.46	neutral	None	None	None	None	N
N/D	0.1987	likely_benign	0.1693	benign	0.291	Stabilizing	0.92	D	0.385	neutral	N	0.433670543	None	None	N
N/E	0.6265	likely_pathogenic	0.5568	ambiguous	0.295	Stabilizing	0.939	D	0.34	neutral	None	None	None	None	N
N/F	0.8144	likely_pathogenic	0.7959	pathogenic	-0.859	Destabilizing	0.997	D	0.477	neutral	None	None	None	None	N
N/G	0.4307	ambiguous	0.403	ambiguous	-0.894	Destabilizing	0.759	D	0.327	neutral	None	None	None	None	N
N/H	0.2614	likely_benign	0.2485	benign	-0.776	Destabilizing	0.996	D	0.41	neutral	D	0.572518071	None	None	N
N/I	0.6909	likely_pathogenic	0.6101	pathogenic	-0.152	Destabilizing	0.988	D	0.462	neutral	D	0.573769035	None	None	N
N/K	0.512	ambiguous	0.4508	ambiguous	0.077	Stabilizing	0.92	D	0.34	neutral	N	0.503160311	None	None	N
N/L	0.5719	likely_pathogenic	0.5489	ambiguous	-0.152	Destabilizing	0.939	D	0.452	neutral	None	None	None	None	N
N/M	0.6116	likely_pathogenic	0.57	pathogenic	0.239	Stabilizing	0.999	D	0.448	neutral	None	None	None	None	N
N/P	0.9806	likely_pathogenic	0.9745	pathogenic	-0.297	Destabilizing	0.991	D	0.436	neutral	None	None	None	None	N
N/Q	0.5387	ambiguous	0.5136	ambiguous	-0.433	Destabilizing	0.991	D	0.379	neutral	None	None	None	None	N
N/R	0.5451	ambiguous	0.5109	ambiguous	0.111	Stabilizing	0.969	D	0.378	neutral	None	None	None	None	N
N/S	0.2059	likely_benign	0.1815	benign	-0.353	Destabilizing	0.31	N	0.105	neutral	N	0.458389998	None	None	N
N/T	0.4907	ambiguous	0.4232	ambiguous	-0.174	Destabilizing	0.704	D	0.331	neutral	D	0.572518071	None	None	N
N/V	0.6985	likely_pathogenic	0.6349	pathogenic	-0.297	Destabilizing	0.939	D	0.485	neutral	None	None	None	None	N
N/W	0.896	likely_pathogenic	0.8866	pathogenic	-0.709	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	N
N/Y	0.2928	likely_benign	0.277	benign	-0.489	Destabilizing	0.996	D	0.465	neutral	D	0.573769035	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.