TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22399	67420;67421;67422	chr2:178580092;178580091;178580090	chr2:179444819;179444818;179444817
N2AB	20758	62497;62498;62499	chr2:178580092;178580091;178580090	chr2:179444819;179444818;179444817
N2A	19831	59716;59717;59718	chr2:178580092;178580091;178580090	chr2:179444819;179444818;179444817
N2B	13334	40225;40226;40227	chr2:178580092;178580091;178580090	chr2:179444819;179444818;179444817
Novex-1	13459	40600;40601;40602	chr2:178580092;178580091;178580090	chr2:179444819;179444818;179444817
Novex-2	13526	40801;40802;40803	chr2:178580092;178580091;178580090	chr2:179444819;179444818;179444817
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: Fn3-50
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.7348
• 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/E	rs1060500421	None	0.999	N	0.616	0.386	0.317084106153	gnomAD-4.0.0	1.59214E-06	None	None	None	None	N	None	0	2.28676E-05	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	0.8548	likely_pathogenic	0.8782	pathogenic	-0.051	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
K/C	0.9433	likely_pathogenic	0.9446	pathogenic	-0.539	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/D	0.95	likely_pathogenic	0.9587	pathogenic	-0.338	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	N
K/E	0.8074	likely_pathogenic	0.8337	pathogenic	-0.361	Destabilizing	0.999	D	0.616	neutral	N	0.506221581	None	None	N
K/F	0.968	likely_pathogenic	0.972	pathogenic	-0.427	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
K/G	0.8781	likely_pathogenic	0.897	pathogenic	-0.155	Destabilizing	1.0	D	0.602	neutral	None	None	None	None	N
K/H	0.7408	likely_pathogenic	0.7361	pathogenic	-0.223	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
K/I	0.8034	likely_pathogenic	0.8487	pathogenic	0.138	Stabilizing	1.0	D	0.713	prob.delet.	N	0.483396653	None	None	N
K/L	0.7507	likely_pathogenic	0.7643	pathogenic	0.138	Stabilizing	1.0	D	0.602	neutral	None	None	None	None	N
K/M	0.6888	likely_pathogenic	0.7102	pathogenic	-0.161	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
K/N	0.894	likely_pathogenic	0.9063	pathogenic	-0.082	Destabilizing	1.0	D	0.649	neutral	N	0.50968596	None	None	N
K/P	0.8709	likely_pathogenic	0.9027	pathogenic	0.097	Stabilizing	1.0	D	0.616	neutral	None	None	None	None	N
K/Q	0.4717	ambiguous	0.4917	ambiguous	-0.232	Destabilizing	1.0	D	0.637	neutral	N	0.512726265	None	None	N
K/R	0.1183	likely_benign	0.1214	benign	-0.173	Destabilizing	0.999	D	0.567	neutral	N	0.473343945	None	None	N
K/S	0.9063	likely_pathogenic	0.9185	pathogenic	-0.448	Destabilizing	0.999	D	0.59	neutral	None	None	None	None	N
K/T	0.7217	likely_pathogenic	0.7607	pathogenic	-0.363	Destabilizing	1.0	D	0.61	neutral	N	0.466809654	None	None	N
K/V	0.785	likely_pathogenic	0.8222	pathogenic	0.097	Stabilizing	1.0	D	0.652	neutral	None	None	None	None	N
K/W	0.9622	likely_pathogenic	0.968	pathogenic	-0.528	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
K/Y	0.92	likely_pathogenic	0.9242	pathogenic	-0.184	Destabilizing	1.0	D	0.681	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.