TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16361	49306;49307;49308	chr2:178614316;178614315;178614314	chr2:179479043;179479042;179479041
N2AB	14720	44383;44384;44385	chr2:178614316;178614315;178614314	chr2:179479043;179479042;179479041
N2A	13793	41602;41603;41604	chr2:178614316;178614315;178614314	chr2:179479043;179479042;179479041
N2B	7296	22111;22112;22113	chr2:178614316;178614315;178614314	chr2:179479043;179479042;179479041
Novex-1	7421	22486;22487;22488	chr2:178614316;178614315;178614314	chr2:179479043;179479042;179479041
Novex-2	7488	22687;22688;22689	chr2:178614316;178614315;178614314	chr2:179479043;179479042;179479041
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-6
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.5106
• 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
T/I	None	None	0.193	N	0.403	0.254	0.258779203287	gnomAD-4.0.0	6.84597E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16001E-05	0
T/R	rs2056892277	None	0.627	N	0.435	0.31	0.330589388543	gnomAD-4.0.0	6.84597E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99818E-07	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
T/A	0.093	likely_benign	0.0953	benign	-0.72	Destabilizing	0.09	N	0.339	neutral	N	0.477071693	None	None	N
T/C	0.3688	ambiguous	0.3822	ambiguous	-0.369	Destabilizing	0.944	D	0.423	neutral	None	None	None	None	N
T/D	0.4687	ambiguous	0.4981	ambiguous	-0.169	Destabilizing	0.388	N	0.412	neutral	None	None	None	None	N
T/E	0.3567	ambiguous	0.3856	ambiguous	-0.185	Destabilizing	0.241	N	0.373	neutral	None	None	None	None	N
T/F	0.3232	likely_benign	0.3567	ambiguous	-0.813	Destabilizing	0.69	D	0.502	neutral	None	None	None	None	N
T/G	0.2453	likely_benign	0.2448	benign	-0.967	Destabilizing	0.241	N	0.432	neutral	None	None	None	None	N
T/H	0.2839	likely_benign	0.2988	benign	-1.246	Destabilizing	0.944	D	0.467	neutral	None	None	None	None	N
T/I	0.2183	likely_benign	0.2492	benign	-0.158	Destabilizing	0.193	N	0.403	neutral	N	0.483575687	None	None	N
T/K	0.225	likely_benign	0.2409	benign	-0.73	Destabilizing	0.193	N	0.367	neutral	N	0.482964009	None	None	N
T/L	0.1337	likely_benign	0.1439	benign	-0.158	Destabilizing	0.043	N	0.385	neutral	None	None	None	None	N
T/M	0.1116	likely_benign	0.1177	benign	0.146	Stabilizing	0.019	N	0.357	neutral	None	None	None	None	N
T/N	0.1569	likely_benign	0.1653	benign	-0.595	Destabilizing	0.241	N	0.383	neutral	None	None	None	None	N
T/P	0.6414	likely_pathogenic	0.6795	pathogenic	-0.313	Destabilizing	0.773	D	0.436	neutral	N	0.471360301	None	None	N
T/Q	0.2513	likely_benign	0.2623	benign	-0.774	Destabilizing	0.69	D	0.435	neutral	None	None	None	None	N
T/R	0.2019	likely_benign	0.2232	benign	-0.468	Destabilizing	0.627	D	0.435	neutral	N	0.47335012	None	None	N
T/S	0.0938	likely_benign	0.0958	benign	-0.86	Destabilizing	0.001	N	0.123	neutral	N	0.422043819	None	None	N
T/V	0.1646	likely_benign	0.1751	benign	-0.313	Destabilizing	0.241	N	0.349	neutral	None	None	None	None	N
T/W	0.6757	likely_pathogenic	0.7071	pathogenic	-0.761	Destabilizing	0.981	D	0.547	neutral	None	None	None	None	N
T/Y	0.3841	ambiguous	0.4079	ambiguous	-0.537	Destabilizing	0.818	D	0.489	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.