TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16492	49699;49700;49701	chr2:178613809;178613808;178613807	chr2:179478536;179478535;179478534
N2AB	14851	44776;44777;44778	chr2:178613809;178613808;178613807	chr2:179478536;179478535;179478534
N2A	13924	41995;41996;41997	chr2:178613809;178613808;178613807	chr2:179478536;179478535;179478534
N2B	7427	22504;22505;22506	chr2:178613809;178613808;178613807	chr2:179478536;179478535;179478534
Novex-1	7552	22879;22880;22881	chr2:178613809;178613808;178613807	chr2:179478536;179478535;179478534
Novex-2	7619	23080;23081;23082	chr2:178613809;178613808;178613807	chr2:179478536;179478535;179478534
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-7
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.1636
• 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
P/A	None	None	0.767	N	0.491	0.184	0.247872288689	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
P/A	0.1177	likely_benign	0.1237	benign	-1.339	Destabilizing	0.767	D	0.491	neutral	N	0.470570512	None	None	N
P/C	0.6215	likely_pathogenic	0.6391	pathogenic	-0.724	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
P/D	0.653	likely_pathogenic	0.6873	pathogenic	-1.082	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
P/E	0.4064	ambiguous	0.4559	ambiguous	-1.126	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
P/F	0.6717	likely_pathogenic	0.7201	pathogenic	-1.221	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
P/G	0.4015	ambiguous	0.4098	ambiguous	-1.608	Destabilizing	0.997	D	0.709	prob.delet.	None	None	None	None	N
P/H	0.4124	ambiguous	0.4379	ambiguous	-1.193	Destabilizing	1.0	D	0.756	deleterious	N	0.493953771	None	None	N
P/I	0.3113	likely_benign	0.3435	ambiguous	-0.717	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
P/K	0.5287	ambiguous	0.5776	pathogenic	-1.036	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
P/L	0.1747	likely_benign	0.2017	benign	-0.717	Destabilizing	0.999	D	0.755	deleterious	N	0.477411372	None	None	N
P/M	0.3295	likely_benign	0.3463	ambiguous	-0.444	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
P/N	0.4861	ambiguous	0.4975	ambiguous	-0.692	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
P/Q	0.3077	likely_benign	0.317	benign	-0.916	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
P/R	0.4351	ambiguous	0.481	ambiguous	-0.479	Destabilizing	0.999	D	0.787	deleterious	N	0.476026771	None	None	N
P/S	0.2105	likely_benign	0.2243	benign	-1.155	Destabilizing	0.998	D	0.724	prob.delet.	N	0.469002517	None	None	N
P/T	0.1239	likely_benign	0.1301	benign	-1.094	Destabilizing	0.999	D	0.749	deleterious	N	0.475029795	None	None	N
P/V	0.222	likely_benign	0.2362	benign	-0.889	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
P/W	0.8271	likely_pathogenic	0.8567	pathogenic	-1.364	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
P/Y	0.6665	likely_pathogenic	0.7094	pathogenic	-1.089	Destabilizing	1.0	D	0.76	deleterious	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.