TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1636	5131;5132;5133	chr2:178776958;178776957;178776956	chr2:179641685;179641684;179641683
N2AB	1636	5131;5132;5133	chr2:178776958;178776957;178776956	chr2:179641685;179641684;179641683
N2A	1636	5131;5132;5133	chr2:178776958;178776957;178776956	chr2:179641685;179641684;179641683
N2B	1590	4993;4994;4995	chr2:178776958;178776957;178776956	chr2:179641685;179641684;179641683
Novex-1	1590	4993;4994;4995	chr2:178776958;178776957;178776956	chr2:179641685;179641684;179641683
Novex-2	1590	4993;4994;4995	chr2:178776958;178776957;178776956	chr2:179641685;179641684;179641683
Novex-3	1636	5131;5132;5133	chr2:178776958;178776957;178776956	chr2:179641685;179641684;179641683

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-7
• Domain position: 81
• Structural Position: 163
• Q(SASA): 0.5524
• 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
A/V	None	None	1.0	N	0.678	0.417	0.52730433808	gnomAD-4.0.0	1.59102E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43336E-05	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
A/C	0.7987	likely_pathogenic	0.7594	pathogenic	-0.862	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
A/D	0.8896	likely_pathogenic	0.862	pathogenic	-0.663	Destabilizing	1.0	D	0.807	deleterious	D	0.675499371	None	None	I
A/E	0.8276	likely_pathogenic	0.7992	pathogenic	-0.821	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
A/F	0.5413	ambiguous	0.4721	ambiguous	-0.952	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	I
A/G	0.4639	ambiguous	0.4134	ambiguous	-0.324	Destabilizing	1.0	D	0.601	neutral	D	0.608593526	None	None	I
A/H	0.8128	likely_pathogenic	0.7851	pathogenic	-0.303	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
A/I	0.6444	likely_pathogenic	0.525	ambiguous	-0.433	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
A/K	0.9483	likely_pathogenic	0.9386	pathogenic	-0.7	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
A/L	0.5572	ambiguous	0.4852	ambiguous	-0.433	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
A/M	0.5681	likely_pathogenic	0.4714	ambiguous	-0.525	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
A/N	0.736	likely_pathogenic	0.6834	pathogenic	-0.398	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	I
A/P	0.9807	likely_pathogenic	0.9754	pathogenic	-0.359	Destabilizing	1.0	D	0.757	deleterious	D	0.714275109	None	None	I
A/Q	0.8022	likely_pathogenic	0.764	pathogenic	-0.691	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	I
A/R	0.893	likely_pathogenic	0.8843	pathogenic	-0.194	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
A/S	0.205	likely_benign	0.1786	benign	-0.565	Destabilizing	1.0	D	0.63	neutral	D	0.577167243	None	None	I
A/T	0.3947	ambiguous	0.3172	benign	-0.65	Destabilizing	1.0	D	0.721	prob.delet.	D	0.617041921	None	None	I
A/V	0.3046	likely_benign	0.2377	benign	-0.359	Destabilizing	1.0	D	0.678	prob.neutral	N	0.508374447	None	None	I
A/W	0.9442	likely_pathogenic	0.9332	pathogenic	-1.062	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
A/Y	0.7637	likely_pathogenic	0.7238	pathogenic	-0.74	Destabilizing	1.0	D	0.797	deleterious	None	None	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.