TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3326	10201;10202;10203	chr2:178764539;178764538;178764537	chr2:179629266;179629265;179629264
N2AB	3326	10201;10202;10203	chr2:178764539;178764538;178764537	chr2:179629266;179629265;179629264
N2A	3326	10201;10202;10203	chr2:178764539;178764538;178764537	chr2:179629266;179629265;179629264
N2B	3280	10063;10064;10065	chr2:178764539;178764538;178764537	chr2:179629266;179629265;179629264
Novex-1	3280	10063;10064;10065	chr2:178764539;178764538;178764537	chr2:179629266;179629265;179629264
Novex-2	3280	10063;10064;10065	chr2:178764539;178764538;178764537	chr2:179629266;179629265;179629264
Novex-3	3326	10201;10202;10203	chr2:178764539;178764538;178764537	chr2:179629266;179629265;179629264

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-23
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.0907
• 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
L/F	None	None	1.0	D	0.809	0.69	0.819994532182	gnomAD-4.0.0	1.59064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-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
L/A	0.966	likely_pathogenic	0.9617	pathogenic	-2.744	Highly Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
L/C	0.96	likely_pathogenic	0.9551	pathogenic	-2.234	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/D	0.9996	likely_pathogenic	0.9996	pathogenic	-3.069	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
L/E	0.9974	likely_pathogenic	0.9973	pathogenic	-2.812	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/F	0.7703	likely_pathogenic	0.7821	pathogenic	-1.727	Destabilizing	1.0	D	0.809	deleterious	D	0.709383927	None	None	N
L/G	0.9953	likely_pathogenic	0.9944	pathogenic	-3.327	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
L/H	0.9941	likely_pathogenic	0.9935	pathogenic	-2.787	Highly Destabilizing	1.0	D	0.849	deleterious	D	0.7988856	None	None	N
L/I	0.3	likely_benign	0.3112	benign	-1.036	Destabilizing	0.999	D	0.579	neutral	D	0.607141204	None	None	N
L/K	0.9953	likely_pathogenic	0.9953	pathogenic	-2.055	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
L/M	0.5353	ambiguous	0.5418	ambiguous	-1.135	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
L/N	0.9976	likely_pathogenic	0.9975	pathogenic	-2.514	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
L/P	0.9976	likely_pathogenic	0.9975	pathogenic	-1.588	Destabilizing	1.0	D	0.865	deleterious	D	0.7988856	None	None	N
L/Q	0.989	likely_pathogenic	0.9875	pathogenic	-2.326	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
L/R	0.9866	likely_pathogenic	0.9854	pathogenic	-1.836	Destabilizing	1.0	D	0.871	deleterious	D	0.7988856	None	None	N
L/S	0.9954	likely_pathogenic	0.9949	pathogenic	-3.254	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/T	0.982	likely_pathogenic	0.9806	pathogenic	-2.835	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/V	0.3477	ambiguous	0.347	ambiguous	-1.588	Destabilizing	0.999	D	0.579	neutral	D	0.606195124	None	None	N
L/W	0.9869	likely_pathogenic	0.9865	pathogenic	-2.098	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
L/Y	0.9881	likely_pathogenic	0.987	pathogenic	-1.825	Destabilizing	1.0	D	0.849	deleterious	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.