TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13769	41530;41531;41532	chr2:178636422;178636421;178636420	chr2:179501149;179501148;179501147
N2AB	12128	36607;36608;36609	chr2:178636422;178636421;178636420	chr2:179501149;179501148;179501147
N2A	11201	33826;33827;33828	chr2:178636422;178636421;178636420	chr2:179501149;179501148;179501147
N2B	4704	14335;14336;14337	chr2:178636422;178636421;178636420	chr2:179501149;179501148;179501147
Novex-1	4829	14710;14711;14712	chr2:178636422;178636421;178636420	chr2:179501149;179501148;179501147
Novex-2	4896	14911;14912;14913	chr2:178636422;178636421;178636420	chr2:179501149;179501148;179501147
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-87
• Domain position: 86
• Structural Position: 169
• Q(SASA): 0.2696
• 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
S/F	rs1306932117	-1.105	0.999	D	0.775	0.518	0.733710926309	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
S/F	rs1306932117	-1.105	0.999	D	0.775	0.518	0.733710926309	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

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
S/A	0.2318	likely_benign	0.2432	benign	-0.752	Destabilizing	0.953	D	0.489	neutral	N	0.48865234	None	None	N
S/C	0.2492	likely_benign	0.2927	benign	-0.488	Destabilizing	0.135	N	0.461	neutral	N	0.504062077	None	None	N
S/D	0.9761	likely_pathogenic	0.979	pathogenic	-0.245	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
S/E	0.9865	likely_pathogenic	0.986	pathogenic	-0.21	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
S/F	0.9552	likely_pathogenic	0.9563	pathogenic	-0.81	Destabilizing	0.999	D	0.775	deleterious	D	0.570883325	None	None	N
S/G	0.5108	ambiguous	0.5038	ambiguous	-1.044	Destabilizing	0.993	D	0.578	neutral	None	None	None	None	N
S/H	0.9472	likely_pathogenic	0.9481	pathogenic	-1.469	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
S/I	0.898	likely_pathogenic	0.9011	pathogenic	-0.073	Destabilizing	0.998	D	0.761	deleterious	None	None	None	None	N
S/K	0.9962	likely_pathogenic	0.9957	pathogenic	-0.589	Destabilizing	0.999	D	0.595	neutral	None	None	None	None	N
S/L	0.759	likely_pathogenic	0.7509	pathogenic	-0.073	Destabilizing	0.985	D	0.689	prob.neutral	None	None	None	None	N
S/M	0.8136	likely_pathogenic	0.8171	pathogenic	0.095	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
S/N	0.8214	likely_pathogenic	0.8336	pathogenic	-0.655	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
S/P	0.9983	likely_pathogenic	0.9982	pathogenic	-0.264	Destabilizing	0.999	D	0.717	prob.delet.	D	0.562742651	None	None	N
S/Q	0.9703	likely_pathogenic	0.9689	pathogenic	-0.724	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
S/R	0.993	likely_pathogenic	0.9927	pathogenic	-0.582	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
S/T	0.2068	likely_benign	0.2171	benign	-0.637	Destabilizing	0.99	D	0.581	neutral	N	0.494387374	None	None	N
S/V	0.7673	likely_pathogenic	0.7816	pathogenic	-0.264	Destabilizing	0.996	D	0.735	prob.delet.	None	None	None	None	N
S/W	0.9777	likely_pathogenic	0.975	pathogenic	-0.81	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
S/Y	0.9318	likely_pathogenic	0.9291	pathogenic	-0.518	Destabilizing	0.999	D	0.779	deleterious	D	0.580827588	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.