TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16169	48730;48731;48732	chr2:178615440;178615439;178615438	chr2:179480167;179480166;179480165
N2AB	14528	43807;43808;43809	chr2:178615440;178615439;178615438	chr2:179480167;179480166;179480165
N2A	13601	41026;41027;41028	chr2:178615440;178615439;178615438	chr2:179480167;179480166;179480165
N2B	7104	21535;21536;21537	chr2:178615440;178615439;178615438	chr2:179480167;179480166;179480165
Novex-1	7229	21910;21911;21912	chr2:178615440;178615439;178615438	chr2:179480167;179480166;179480165
Novex-2	7296	22111;22112;22113	chr2:178615440;178615439;178615438	chr2:179480167;179480166;179480165
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-5
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.1242
• 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
A/T	None	None	0.008	N	0.397	0.111	0.225902525712	gnomAD-4.0.0	1.59423E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86434E-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
A/C	0.4734	ambiguous	0.5329	ambiguous	-1.11	Destabilizing	0.989	D	0.605	neutral	None	None	None	None	N
A/D	0.6368	likely_pathogenic	0.682	pathogenic	-1.79	Destabilizing	0.901	D	0.62	neutral	N	0.461963488	None	None	N
A/E	0.4031	ambiguous	0.4475	ambiguous	-1.892	Destabilizing	0.775	D	0.644	neutral	None	None	None	None	N
A/F	0.6423	likely_pathogenic	0.6838	pathogenic	-1.365	Destabilizing	0.961	D	0.627	neutral	None	None	None	None	N
A/G	0.1254	likely_benign	0.1468	benign	-0.868	Destabilizing	0.349	N	0.621	neutral	N	0.482193121	None	None	N
A/H	0.5985	likely_pathogenic	0.6382	pathogenic	-0.843	Destabilizing	0.996	D	0.626	neutral	None	None	None	None	N
A/I	0.4798	ambiguous	0.5307	ambiguous	-0.601	Destabilizing	0.858	D	0.599	neutral	None	None	None	None	N
A/K	0.2915	likely_benign	0.312	benign	-0.946	Destabilizing	0.775	D	0.637	neutral	None	None	None	None	N
A/L	0.3831	ambiguous	0.4174	ambiguous	-0.601	Destabilizing	0.633	D	0.632	neutral	None	None	None	None	N
A/M	0.4254	ambiguous	0.469	ambiguous	-0.415	Destabilizing	0.989	D	0.588	neutral	None	None	None	None	N
A/N	0.4238	ambiguous	0.4817	ambiguous	-0.829	Destabilizing	0.923	D	0.611	neutral	None	None	None	None	N
A/P	0.3532	ambiguous	0.4417	ambiguous	-0.618	Destabilizing	0.949	D	0.591	neutral	N	0.48146409	None	None	N
A/Q	0.3433	ambiguous	0.3761	ambiguous	-1.195	Destabilizing	0.961	D	0.619	neutral	None	None	None	None	N
A/R	0.2996	likely_benign	0.3043	benign	-0.448	Destabilizing	0.923	D	0.59	neutral	None	None	None	None	N
A/S	0.1024	likely_benign	0.11	benign	-1.0	Destabilizing	0.014	N	0.214	neutral	N	0.442470087	None	None	N
A/T	0.1607	likely_benign	0.1756	benign	-1.041	Destabilizing	0.008	N	0.397	neutral	N	0.471435902	None	None	N
A/V	0.2537	likely_benign	0.2904	benign	-0.618	Destabilizing	0.565	D	0.653	neutral	D	0.535376177	None	None	N
A/W	0.8932	likely_pathogenic	0.9047	pathogenic	-1.537	Destabilizing	0.996	D	0.671	neutral	None	None	None	None	N
A/Y	0.7078	likely_pathogenic	0.7455	pathogenic	-1.146	Destabilizing	0.961	D	0.639	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.