TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15507	46744;46745;46746	chr2:178619798;178619797;178619796	chr2:179484525;179484524;179484523
N2AB	13866	41821;41822;41823	chr2:178619798;178619797;178619796	chr2:179484525;179484524;179484523
N2A	12939	39040;39041;39042	chr2:178619798;178619797;178619796	chr2:179484525;179484524;179484523
N2B	6442	19549;19550;19551	chr2:178619798;178619797;178619796	chr2:179484525;179484524;179484523
Novex-1	6567	19924;19925;19926	chr2:178619798;178619797;178619796	chr2:179484525;179484524;179484523
Novex-2	6634	20125;20126;20127	chr2:178619798;178619797;178619796	chr2:179484525;179484524;179484523
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-107
• Domain position: 28
• Structural Position: 43
• Q(SASA): 0.95
• 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
K/N	rs781291079	0.25	0.549	N	0.385	0.164	0.112648838833	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	8.93E-06	0
K/N	rs781291079	0.25	0.549	N	0.385	0.164	0.112648838833	gnomAD-4.0.0	3.42382E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.7002E-06	1.16012E-05	1.65865E-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
K/A	0.2698	likely_benign	0.3329	benign	-0.019	Destabilizing	0.25	N	0.431	neutral	None	None	None	None	N
K/C	0.6596	likely_pathogenic	0.7825	pathogenic	-0.486	Destabilizing	0.992	D	0.421	neutral	None	None	None	None	N
K/D	0.3478	ambiguous	0.4003	ambiguous	-0.341	Destabilizing	0.617	D	0.485	neutral	None	None	None	None	N
K/E	0.1769	likely_benign	0.2137	benign	-0.362	Destabilizing	0.334	N	0.391	neutral	N	0.461009681	None	None	N
K/F	0.7858	likely_pathogenic	0.8442	pathogenic	-0.387	Destabilizing	0.972	D	0.425	neutral	None	None	None	None	N
K/G	0.2031	likely_benign	0.29	benign	-0.129	Destabilizing	0.002	N	0.251	neutral	None	None	None	None	N
K/H	0.2498	likely_benign	0.2989	benign	-0.21	Destabilizing	0.92	D	0.431	neutral	None	None	None	None	N
K/I	0.547	ambiguous	0.5888	pathogenic	0.187	Stabilizing	0.92	D	0.437	neutral	None	None	None	None	N
K/L	0.4267	ambiguous	0.5004	ambiguous	0.187	Stabilizing	0.617	D	0.493	neutral	None	None	None	None	N
K/M	0.286	likely_benign	0.3593	ambiguous	-0.142	Destabilizing	0.963	D	0.427	neutral	N	0.456892936	None	None	N
K/N	0.2518	likely_benign	0.3101	benign	-0.025	Destabilizing	0.549	D	0.385	neutral	N	0.440136548	None	None	N
K/P	0.8023	likely_pathogenic	0.7874	pathogenic	0.14	Stabilizing	0.972	D	0.443	neutral	None	None	None	None	N
K/Q	0.1291	likely_benign	0.155	benign	-0.175	Destabilizing	0.549	D	0.409	neutral	N	0.482079375	None	None	N
K/R	0.0796	likely_benign	0.0837	benign	-0.138	Destabilizing	0.001	N	0.223	neutral	N	0.4247239	None	None	N
K/S	0.2932	likely_benign	0.3657	ambiguous	-0.38	Destabilizing	0.4	N	0.371	neutral	None	None	None	None	N
K/T	0.1708	likely_benign	0.1936	benign	-0.292	Destabilizing	0.549	D	0.478	neutral	N	0.434814902	None	None	N
K/V	0.4467	ambiguous	0.4944	ambiguous	0.14	Stabilizing	0.766	D	0.465	neutral	None	None	None	None	N
K/W	0.7869	likely_pathogenic	0.8431	pathogenic	-0.493	Destabilizing	0.992	D	0.437	neutral	None	None	None	None	N
K/Y	0.6215	likely_pathogenic	0.7053	pathogenic	-0.146	Destabilizing	0.972	D	0.447	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.