TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8865	26818;26819;26820	chr2:178714065;178714064;178714063	chr2:179578792;179578791;179578790
N2AB	8548	25867;25868;25869	chr2:178714065;178714064;178714063	chr2:179578792;179578791;179578790
N2A	7621	23086;23087;23088	chr2:178714065;178714064;178714063	chr2:179578792;179578791;179578790
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-74
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1168
• 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	rs765507696	-1.24	0.978	N	0.721	0.316	0.220303561663	gnomAD-2.1.1	5.72E-05	None	None	None	None	N	None	0	0	None	0	8.23638E-04	None	0	None	0	0	0
K/N	rs765507696	-1.24	0.978	N	0.721	0.316	0.220303561663	gnomAD-3.1.2	4.6E-05	None	None	None	None	N	None	0	0	0	0	1.35031E-03	None	0	0	0	0	0
K/N	rs765507696	-1.24	0.978	N	0.721	0.316	0.220303561663	gnomAD-4.0.0	1.61138E-05	None	None	None	None	N	None	0	0	None	0	5.79865E-04	None	0	0	0	0	0
K/R	rs1165281102	-0.624	0.085	N	0.371	0.18	0.208816687407	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
K/R	rs1165281102	-0.624	0.085	N	0.371	0.18	0.208816687407	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs1165281102	-0.624	0.085	N	0.371	0.18	0.208816687407	gnomAD-4.0.0	7.68835E-06	None	None	None	None	N	None	1.69165E-05	1.69572E-05	None	0	0	None	0	0	9.57387E-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
K/A	0.9131	likely_pathogenic	0.9384	pathogenic	-1.163	Destabilizing	0.944	D	0.56	neutral	None	None	None	None	N
K/C	0.8732	likely_pathogenic	0.8989	pathogenic	-1.125	Destabilizing	0.999	D	0.855	deleterious	None	None	None	None	N
K/D	0.9888	likely_pathogenic	0.9944	pathogenic	-0.442	Destabilizing	0.983	D	0.771	deleterious	None	None	None	None	N
K/E	0.7948	likely_pathogenic	0.8538	pathogenic	-0.241	Destabilizing	0.865	D	0.518	neutral	D	0.523360464	None	None	N
K/F	0.9262	likely_pathogenic	0.9467	pathogenic	-0.754	Destabilizing	0.999	D	0.853	deleterious	None	None	None	None	N
K/G	0.9633	likely_pathogenic	0.978	pathogenic	-1.588	Destabilizing	0.983	D	0.729	prob.delet.	None	None	None	None	N
K/H	0.527	ambiguous	0.6196	pathogenic	-1.745	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
K/I	0.7129	likely_pathogenic	0.7523	pathogenic	-0.01	Destabilizing	0.992	D	0.859	deleterious	None	None	None	None	N
K/L	0.6614	likely_pathogenic	0.723	pathogenic	-0.01	Destabilizing	0.983	D	0.729	prob.delet.	None	None	None	None	N
K/M	0.5739	likely_pathogenic	0.6236	pathogenic	-0.158	Destabilizing	0.999	D	0.78	deleterious	D	0.541211229	None	None	N
K/N	0.9505	likely_pathogenic	0.9677	pathogenic	-0.982	Destabilizing	0.978	D	0.721	prob.delet.	N	0.509281907	None	None	N
K/P	0.9944	likely_pathogenic	0.9972	pathogenic	-0.367	Destabilizing	0.992	D	0.787	deleterious	None	None	None	None	N
K/Q	0.4127	ambiguous	0.4855	ambiguous	-0.886	Destabilizing	0.978	D	0.71	prob.delet.	N	0.499887385	None	None	N
K/R	0.0891	likely_benign	0.1	benign	-0.684	Destabilizing	0.085	N	0.371	neutral	N	0.458128558	None	None	N
K/S	0.9448	likely_pathogenic	0.9637	pathogenic	-1.753	Destabilizing	0.944	D	0.578	neutral	None	None	None	None	N
K/T	0.8715	likely_pathogenic	0.895	pathogenic	-1.299	Destabilizing	0.978	D	0.739	prob.delet.	N	0.50672424	None	None	N
K/V	0.7209	likely_pathogenic	0.7591	pathogenic	-0.367	Destabilizing	0.983	D	0.793	deleterious	None	None	None	None	N
K/W	0.8818	likely_pathogenic	0.9326	pathogenic	-0.592	Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
K/Y	0.8464	likely_pathogenic	0.8939	pathogenic	-0.294	Destabilizing	0.997	D	0.85	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.