TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29524	88795;88796;88797	chr2:178554889;178554888;178554887	chr2:179419616;179419615;179419614
N2AB	27883	83872;83873;83874	chr2:178554889;178554888;178554887	chr2:179419616;179419615;179419614
N2A	26956	81091;81092;81093	chr2:178554889;178554888;178554887	chr2:179419616;179419615;179419614
N2B	20459	61600;61601;61602	chr2:178554889;178554888;178554887	chr2:179419616;179419615;179419614
Novex-1	20584	61975;61976;61977	chr2:178554889;178554888;178554887	chr2:179419616;179419615;179419614
Novex-2	20651	62176;62177;62178	chr2:178554889;178554888;178554887	chr2:179419616;179419615;179419614
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: Ig-146
• Domain position: 81
• Structural Position: 169
• Q(SASA): 0.1628
• 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/V	rs1700784801	None	0.733	N	0.387	0.298	0.479893544335	gnomAD-4.0.0	1.59115E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02425E-05

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	0.5511	ambiguous	0.5298	ambiguous	-0.898	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
A/D	0.7192	likely_pathogenic	0.6512	pathogenic	-0.34	Destabilizing	0.998	D	0.813	deleterious	N	0.509258449	None	None	N
A/E	0.5712	likely_pathogenic	0.4876	ambiguous	-0.448	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
A/F	0.6213	likely_pathogenic	0.565	pathogenic	-0.759	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
A/G	0.2281	likely_benign	0.212	benign	-0.522	Destabilizing	0.217	N	0.397	neutral	N	0.496029266	None	None	N
A/H	0.7368	likely_pathogenic	0.6759	pathogenic	-0.5	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
A/I	0.4806	ambiguous	0.4383	ambiguous	-0.234	Destabilizing	0.995	D	0.742	deleterious	None	None	None	None	N
A/K	0.6781	likely_pathogenic	0.5853	pathogenic	-0.766	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
A/L	0.4253	ambiguous	0.3852	ambiguous	-0.234	Destabilizing	0.983	D	0.609	neutral	None	None	None	None	N
A/M	0.3929	ambiguous	0.3596	ambiguous	-0.39	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
A/N	0.638	likely_pathogenic	0.5829	pathogenic	-0.506	Destabilizing	0.999	D	0.821	deleterious	None	None	None	None	N
A/P	0.9848	likely_pathogenic	0.977	pathogenic	-0.249	Destabilizing	0.999	D	0.793	deleterious	D	0.528212078	None	None	N
A/Q	0.5596	ambiguous	0.4945	ambiguous	-0.709	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
A/R	0.6328	likely_pathogenic	0.5421	ambiguous	-0.355	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
A/S	0.155	likely_benign	0.1466	benign	-0.807	Destabilizing	0.989	D	0.584	neutral	D	0.535579774	None	None	N
A/T	0.1252	likely_benign	0.1152	benign	-0.815	Destabilizing	0.989	D	0.675	neutral	N	0.49374786	None	None	N
A/V	0.2126	likely_benign	0.1946	benign	-0.249	Destabilizing	0.733	D	0.387	neutral	N	0.52126647	None	None	N
A/W	0.9345	likely_pathogenic	0.9114	pathogenic	-0.947	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/Y	0.7483	likely_pathogenic	0.7004	pathogenic	-0.578	Destabilizing	1.0	D	0.827	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.