TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10082	30469;30470;30471	chr2:178702643;178702642;178702641	chr2:179567370;179567369;179567368
N2AB	9765	29518;29519;29520	chr2:178702643;178702642;178702641	chr2:179567370;179567369;179567368
N2A	8838	26737;26738;26739	chr2:178702643;178702642;178702641	chr2:179567370;179567369;179567368
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-86
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.6202
• 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/T	rs2075208868	None	0.83	None	0.761	0.243	0.336647302497	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/T	rs2075208868	None	0.83	None	0.761	0.243	0.336647302497	gnomAD-4.0.0	6.57004E-06	None	None	None	None	N	None	2.41371E-05	0	None	0	0	None	0	0	0	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	0.9428	likely_pathogenic	0.9473	pathogenic	-0.392	Destabilizing	0.648	D	0.625	neutral	None	None	None	None	N
K/C	0.9591	likely_pathogenic	0.973	pathogenic	-0.291	Destabilizing	0.993	D	0.734	prob.delet.	None	None	None	None	N
K/D	0.9766	likely_pathogenic	0.9806	pathogenic	-0.249	Destabilizing	0.866	D	0.78	deleterious	None	None	None	None	N
K/E	0.7633	likely_pathogenic	0.775	pathogenic	-0.162	Destabilizing	0.41	N	0.547	neutral	None	None	None	None	N
K/F	0.9965	likely_pathogenic	0.9974	pathogenic	-0.122	Destabilizing	0.98	D	0.716	prob.delet.	None	None	None	None	N
K/G	0.9284	likely_pathogenic	0.9492	pathogenic	-0.748	Destabilizing	0.866	D	0.667	neutral	None	None	None	None	N
K/H	0.725	likely_pathogenic	0.7693	pathogenic	-1.165	Destabilizing	0.98	D	0.738	prob.delet.	None	None	None	None	N
K/I	0.9647	likely_pathogenic	0.9743	pathogenic	0.522	Stabilizing	0.929	D	0.74	deleterious	None	None	None	None	N
K/L	0.9439	likely_pathogenic	0.9551	pathogenic	0.522	Stabilizing	0.866	D	0.667	neutral	None	None	None	None	N
K/M	0.9184	likely_pathogenic	0.9283	pathogenic	0.489	Stabilizing	0.991	D	0.739	prob.delet.	None	None	None	None	N
K/N	0.93	likely_pathogenic	0.9381	pathogenic	-0.326	Destabilizing	0.83	D	0.695	prob.neutral	None	None	None	None	N
K/P	0.995	likely_pathogenic	0.997	pathogenic	0.248	Stabilizing	0.929	D	0.781	deleterious	None	None	None	None	N
K/Q	0.439	ambiguous	0.4635	ambiguous	-0.427	Destabilizing	0.83	D	0.69	prob.neutral	None	None	None	None	N
K/R	0.0869	likely_benign	0.098	benign	-0.59	Destabilizing	0.01	N	0.267	neutral	None	None	None	None	N
K/S	0.9404	likely_pathogenic	0.9459	pathogenic	-0.89	Destabilizing	0.648	D	0.607	neutral	None	None	None	None	N
K/T	0.8487	likely_pathogenic	0.8631	pathogenic	-0.61	Destabilizing	0.83	D	0.761	deleterious	None	None	None	None	N
K/V	0.9346	likely_pathogenic	0.9517	pathogenic	0.248	Stabilizing	0.866	D	0.754	deleterious	None	None	None	None	N
K/W	0.9849	likely_pathogenic	0.9894	pathogenic	-0.041	Destabilizing	0.993	D	0.74	deleterious	None	None	None	None	N
K/Y	0.9785	likely_pathogenic	0.9835	pathogenic	0.245	Stabilizing	0.929	D	0.739	prob.delet.	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.