TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4951	15076;15077;15078	chr2:178735595;178735594;178735593	chr2:179600322;179600321;179600320
N2AB	4634	14125;14126;14127	chr2:178735595;178735594;178735593	chr2:179600322;179600321;179600320
N2A	3707	11344;11345;11346	chr2:178735595;178735594;178735593	chr2:179600322;179600321;179600320
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: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-32
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.4734
• 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
K/R	rs1235893686	0.028	0.98	N	0.442	0.287	0.549671953984	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
K/R	rs1235893686	0.028	0.98	N	0.442	0.287	0.549671953984	gnomAD-4.0.0	2.05335E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99573E-07	2.32072E-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
K/A	0.5175	ambiguous	0.5793	pathogenic	-0.379	Destabilizing	0.985	D	0.403	neutral	None	None	None	None	I
K/C	0.7878	likely_pathogenic	0.8295	pathogenic	-0.398	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
K/D	0.8098	likely_pathogenic	0.8461	pathogenic	0.074	Stabilizing	0.971	D	0.439	neutral	None	None	None	None	I
K/E	0.4248	ambiguous	0.4791	ambiguous	0.176	Stabilizing	0.4	N	0.278	neutral	N	0.509431111	None	None	I
K/F	0.8597	likely_pathogenic	0.8831	pathogenic	-0.082	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	I
K/G	0.5324	ambiguous	0.599	pathogenic	-0.729	Destabilizing	0.993	D	0.433	neutral	None	None	None	None	I
K/H	0.3873	ambiguous	0.4246	ambiguous	-0.975	Destabilizing	1.0	D	0.475	neutral	None	None	None	None	I
K/I	0.6373	likely_pathogenic	0.6765	pathogenic	0.514	Stabilizing	0.994	D	0.652	neutral	D	0.584508556	None	None	I
K/L	0.5243	ambiguous	0.5702	pathogenic	0.514	Stabilizing	0.985	D	0.435	neutral	None	None	None	None	I
K/M	0.43	ambiguous	0.4732	ambiguous	0.272	Stabilizing	1.0	D	0.479	neutral	None	None	None	None	I
K/N	0.6428	likely_pathogenic	0.6819	pathogenic	-0.26	Destabilizing	0.997	D	0.406	neutral	N	0.511504695	None	None	I
K/P	0.8916	likely_pathogenic	0.9098	pathogenic	0.247	Stabilizing	0.999	D	0.471	neutral	None	None	None	None	I
K/Q	0.21	likely_benign	0.2333	benign	-0.292	Destabilizing	0.994	D	0.453	neutral	N	0.397572079	None	None	I
K/R	0.0797	likely_benign	0.0847	benign	-0.451	Destabilizing	0.98	D	0.442	neutral	N	0.51246786	None	None	I
K/S	0.579	likely_pathogenic	0.6373	pathogenic	-0.878	Destabilizing	0.971	D	0.427	neutral	None	None	None	None	I
K/T	0.3388	likely_benign	0.3769	ambiguous	-0.572	Destabilizing	0.4	N	0.303	neutral	N	0.508159963	None	None	I
K/V	0.5153	ambiguous	0.5578	ambiguous	0.247	Stabilizing	0.996	D	0.441	neutral	None	None	None	None	I
K/W	0.8287	likely_pathogenic	0.8591	pathogenic	-0.002	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
K/Y	0.7596	likely_pathogenic	0.79	pathogenic	0.282	Stabilizing	0.999	D	0.6	neutral	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.