TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31038	93337;93338;93339	chr2:178548514;178548513;178548512	chr2:179413241;179413240;179413239
N2AB	29397	88414;88415;88416	chr2:178548514;178548513;178548512	chr2:179413241;179413240;179413239
N2A	28470	85633;85634;85635	chr2:178548514;178548513;178548512	chr2:179413241;179413240;179413239
N2B	21973	66142;66143;66144	chr2:178548514;178548513;178548512	chr2:179413241;179413240;179413239
Novex-1	22098	66517;66518;66519	chr2:178548514;178548513;178548512	chr2:179413241;179413240;179413239
Novex-2	22165	66718;66719;66720	chr2:178548514;178548513;178548512	chr2:179413241;179413240;179413239
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-114
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.5237
• Predicted PPI site: I

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
D/N	None	None	1.0	N	0.666	0.368	0.340273420219	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	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
D/A	0.4968	ambiguous	0.3631	ambiguous	-0.336	Destabilizing	1.0	D	0.801	deleterious	N	0.499106394	None	None	I
D/C	0.9169	likely_pathogenic	0.8552	pathogenic	-0.171	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	I
D/E	0.258	likely_benign	0.1928	benign	-0.406	Destabilizing	1.0	D	0.471	neutral	N	0.412639416	None	None	I
D/F	0.8968	likely_pathogenic	0.8436	pathogenic	-0.058	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
D/G	0.4924	ambiguous	0.3497	ambiguous	-0.601	Destabilizing	1.0	D	0.807	deleterious	N	0.475434163	None	None	I
D/H	0.6778	likely_pathogenic	0.533	ambiguous	-0.052	Destabilizing	1.0	D	0.785	deleterious	N	0.4968301	None	None	I
D/I	0.8094	likely_pathogenic	0.7057	pathogenic	0.335	Stabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
D/K	0.7974	likely_pathogenic	0.6734	pathogenic	-0.073	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
D/L	0.7725	likely_pathogenic	0.6601	pathogenic	0.335	Stabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
D/M	0.8686	likely_pathogenic	0.7988	pathogenic	0.465	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
D/N	0.2698	likely_benign	0.2035	benign	-0.4	Destabilizing	1.0	D	0.666	neutral	N	0.489966836	None	None	I
D/P	0.9555	likely_pathogenic	0.9215	pathogenic	0.136	Stabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
D/Q	0.678	likely_pathogenic	0.5301	ambiguous	-0.31	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
D/R	0.8172	likely_pathogenic	0.7054	pathogenic	0.185	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
D/S	0.3888	ambiguous	0.2812	benign	-0.564	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	I
D/T	0.6138	likely_pathogenic	0.4771	ambiguous	-0.355	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
D/V	0.6045	likely_pathogenic	0.473	ambiguous	0.136	Stabilizing	1.0	D	0.854	deleterious	N	0.472547327	None	None	I
D/W	0.9678	likely_pathogenic	0.951	pathogenic	0.101	Stabilizing	1.0	D	0.83	deleterious	None	None	None	None	I
D/Y	0.5447	ambiguous	0.4393	ambiguous	0.172	Stabilizing	1.0	D	0.844	deleterious	N	0.477333493	None	None	I

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.