TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19494	58705;58706;58707	chr2:178593820;178593819;178593818	chr2:179458547;179458546;179458545
N2AB	17853	53782;53783;53784	chr2:178593820;178593819;178593818	chr2:179458547;179458546;179458545
N2A	16926	51001;51002;51003	chr2:178593820;178593819;178593818	chr2:179458547;179458546;179458545
N2B	10429	31510;31511;31512	chr2:178593820;178593819;178593818	chr2:179458547;179458546;179458545
Novex-1	10554	31885;31886;31887	chr2:178593820;178593819;178593818	chr2:179458547;179458546;179458545
Novex-2	10621	32086;32087;32088	chr2:178593820;178593819;178593818	chr2:179458547;179458546;179458545
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: Fn3-29
• Domain position: 16
• Structural Position: 17
• Q(SASA): 0.4186
• 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/R	None	None	0.011	N	0.105	0.08	0.273070737957	gnomAD-4.0.0	1.59297E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85976E-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	0.416	ambiguous	0.41	ambiguous	-0.335	Destabilizing	0.919	D	0.531	neutral	None	None	None	None	N
K/C	0.6917	likely_pathogenic	0.7439	pathogenic	-0.379	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
K/D	0.7969	likely_pathogenic	0.7795	pathogenic	-0.285	Destabilizing	0.988	D	0.529	neutral	None	None	None	None	N
K/E	0.3248	likely_benign	0.3283	benign	-0.242	Destabilizing	0.896	D	0.485	neutral	N	0.490137407	None	None	N
K/F	0.9345	likely_pathogenic	0.9502	pathogenic	-0.343	Destabilizing	0.996	D	0.722	prob.delet.	None	None	None	None	N
K/G	0.5005	ambiguous	0.496	ambiguous	-0.63	Destabilizing	0.959	D	0.59	neutral	None	None	None	None	N
K/H	0.4575	ambiguous	0.516	ambiguous	-1.089	Destabilizing	0.988	D	0.561	neutral	None	None	None	None	N
K/I	0.7295	likely_pathogenic	0.7248	pathogenic	0.392	Stabilizing	0.984	D	0.706	prob.neutral	N	0.495171032	None	None	N
K/L	0.7081	likely_pathogenic	0.7195	pathogenic	0.392	Stabilizing	0.919	D	0.59	neutral	None	None	None	None	N
K/M	0.4886	ambiguous	0.5046	ambiguous	0.426	Stabilizing	0.999	D	0.553	neutral	None	None	None	None	N
K/N	0.633	likely_pathogenic	0.634	pathogenic	-0.176	Destabilizing	0.896	D	0.478	neutral	N	0.51324634	None	None	N
K/P	0.8533	likely_pathogenic	0.8217	pathogenic	0.18	Stabilizing	0.996	D	0.559	neutral	None	None	None	None	N
K/Q	0.2076	likely_benign	0.2233	benign	-0.413	Destabilizing	0.896	D	0.526	neutral	N	0.519057592	None	None	N
K/R	0.0675	likely_benign	0.0756	benign	-0.397	Destabilizing	0.011	N	0.105	neutral	N	0.448216214	None	None	N
K/S	0.4703	ambiguous	0.4794	ambiguous	-0.744	Destabilizing	0.919	D	0.442	neutral	None	None	None	None	N
K/T	0.3882	ambiguous	0.3692	ambiguous	-0.527	Destabilizing	0.946	D	0.522	neutral	N	0.467441538	None	None	N
K/V	0.6151	likely_pathogenic	0.6023	pathogenic	0.18	Stabilizing	0.988	D	0.573	neutral	None	None	None	None	N
K/W	0.8819	likely_pathogenic	0.9095	pathogenic	-0.236	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
K/Y	0.8319	likely_pathogenic	0.8598	pathogenic	0.093	Stabilizing	0.996	D	0.679	prob.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.