TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30320	91183;91184;91185	chr2:178551942;178551941;178551940	chr2:179416669;179416668;179416667
N2AB	28679	86260;86261;86262	chr2:178551942;178551941;178551940	chr2:179416669;179416668;179416667
N2A	27752	83479;83480;83481	chr2:178551942;178551941;178551940	chr2:179416669;179416668;179416667
N2B	21255	63988;63989;63990	chr2:178551942;178551941;178551940	chr2:179416669;179416668;179416667
Novex-1	21380	64363;64364;64365	chr2:178551942;178551941;178551940	chr2:179416669;179416668;179416667
Novex-2	21447	64564;64565;64566	chr2:178551942;178551941;178551940	chr2:179416669;179416668;179416667
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-108
• Domain position: 97
• Structural Position: 132
• Q(SASA): 1.1259
• 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
H/R	rs1244743041	0.028	0.999	D	0.672	0.413	0.360565625551	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
H/R	rs1244743041	0.028	0.999	D	0.672	0.413	0.360565625551	gnomAD-4.0.0	6.19918E-06	None	None	None	None	N	None	2.6698E-05	0	None	0	0	None	0	0	6.78369E-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
H/A	0.8195	likely_pathogenic	0.8841	pathogenic	0.598	Stabilizing	0.998	D	0.513	neutral	None	None	None	None	N
H/C	0.5687	likely_pathogenic	0.6459	pathogenic	1.092	Stabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
H/D	0.5206	ambiguous	0.5922	pathogenic	0.077	Stabilizing	0.999	D	0.635	neutral	N	0.472928231	None	None	N
H/E	0.7681	likely_pathogenic	0.8508	pathogenic	0.103	Stabilizing	0.998	D	0.587	neutral	None	None	None	None	N
H/F	0.6611	likely_pathogenic	0.7543	pathogenic	1.242	Stabilizing	0.999	D	0.681	prob.neutral	None	None	None	None	N
H/G	0.7869	likely_pathogenic	0.8514	pathogenic	0.308	Stabilizing	0.998	D	0.512	neutral	None	None	None	None	N
H/I	0.8767	likely_pathogenic	0.9403	pathogenic	1.333	Stabilizing	0.999	D	0.814	deleterious	None	None	None	None	N
H/K	0.8653	likely_pathogenic	0.9125	pathogenic	0.586	Stabilizing	0.999	D	0.625	neutral	None	None	None	None	N
H/L	0.4054	ambiguous	0.5287	ambiguous	1.333	Stabilizing	0.999	D	0.739	deleterious	N	0.520258031	None	None	N
H/M	0.8596	likely_pathogenic	0.909	pathogenic	1.038	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
H/N	0.2116	likely_benign	0.2643	benign	0.622	Stabilizing	0.997	D	0.588	neutral	N	0.488993762	None	None	N
H/P	0.3143	likely_benign	0.4251	ambiguous	1.115	Stabilizing	0.999	D	0.752	deleterious	N	0.486561248	None	None	N
H/Q	0.6616	likely_pathogenic	0.7769	pathogenic	0.725	Stabilizing	0.999	D	0.687	prob.delet.	N	0.480013882	None	None	N
H/R	0.6823	likely_pathogenic	0.793	pathogenic	-0.121	Destabilizing	0.999	D	0.672	prob.neutral	D	0.528416155	None	None	N
H/S	0.5847	likely_pathogenic	0.6467	pathogenic	0.795	Stabilizing	0.999	D	0.611	neutral	None	None	None	None	N
H/T	0.8054	likely_pathogenic	0.864	pathogenic	0.919	Stabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
H/V	0.8487	likely_pathogenic	0.9163	pathogenic	1.115	Stabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
H/W	0.6886	likely_pathogenic	0.7571	pathogenic	1.182	Stabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
H/Y	0.2022	likely_benign	0.2884	benign	1.488	Stabilizing	0.997	D	0.55	neutral	N	0.487801683	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.