TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34262	103009;103010;103011	chr2:178533831;178533830;178533829	chr2:179398558;179398557;179398556
N2AB	32621	98086;98087;98088	chr2:178533831;178533830;178533829	chr2:179398558;179398557;179398556
N2A	31694	95305;95306;95307	chr2:178533831;178533830;178533829	chr2:179398558;179398557;179398556
N2B	25197	75814;75815;75816	chr2:178533831;178533830;178533829	chr2:179398558;179398557;179398556
Novex-1	25322	76189;76190;76191	chr2:178533831;178533830;178533829	chr2:179398558;179398557;179398556
Novex-2	25389	76390;76391;76392	chr2:178533831;178533830;178533829	chr2:179398558;179398557;179398556
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-161
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.4985
• 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/M	None	None	0.999	N	0.613	0.169	0.484985748688	gnomAD-4.0.0	6.8416E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99408E-07	0	0
L/V	None	None	0.989	N	0.443	0.164	0.511047945453	gnomAD-4.0.0	6.8416E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99408E-07	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
L/A	0.8278	likely_pathogenic	0.8572	pathogenic	-0.574	Destabilizing	0.966	D	0.499	neutral	None	None	None	None	N
L/C	0.9115	likely_pathogenic	0.9514	pathogenic	-0.677	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	N
L/D	0.9871	likely_pathogenic	0.9894	pathogenic	0.087	Stabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
L/E	0.9106	likely_pathogenic	0.9255	pathogenic	0.012	Stabilizing	0.998	D	0.673	neutral	None	None	None	None	N
L/F	0.5124	ambiguous	0.6252	pathogenic	-0.474	Destabilizing	0.999	D	0.604	neutral	None	None	None	None	N
L/G	0.9677	likely_pathogenic	0.9742	pathogenic	-0.752	Destabilizing	0.15	N	0.418	neutral	None	None	None	None	N
L/H	0.824	likely_pathogenic	0.8868	pathogenic	-0.001	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
L/I	0.2721	likely_benign	0.3027	benign	-0.225	Destabilizing	0.997	D	0.448	neutral	None	None	None	None	N
L/K	0.8374	likely_pathogenic	0.853	pathogenic	-0.307	Destabilizing	0.998	D	0.671	neutral	None	None	None	None	N
L/M	0.3151	likely_benign	0.3625	ambiguous	-0.364	Destabilizing	0.999	D	0.613	neutral	N	0.512625557	None	None	N
L/N	0.9283	likely_pathogenic	0.945	pathogenic	-0.16	Destabilizing	0.995	D	0.677	prob.neutral	None	None	None	None	N
L/P	0.986	likely_pathogenic	0.9846	pathogenic	-0.308	Destabilizing	0.999	D	0.679	prob.neutral	N	0.495745642	None	None	N
L/Q	0.7243	likely_pathogenic	0.7799	pathogenic	-0.339	Destabilizing	0.999	D	0.655	neutral	N	0.431697684	None	None	N
L/R	0.7405	likely_pathogenic	0.7944	pathogenic	0.196	Stabilizing	0.997	D	0.666	neutral	N	0.469680069	None	None	N
L/S	0.8925	likely_pathogenic	0.9261	pathogenic	-0.666	Destabilizing	0.995	D	0.613	neutral	None	None	None	None	N
L/T	0.8369	likely_pathogenic	0.8659	pathogenic	-0.627	Destabilizing	0.998	D	0.633	neutral	None	None	None	None	N
L/V	0.3265	likely_benign	0.361	ambiguous	-0.308	Destabilizing	0.989	D	0.443	neutral	N	0.471085579	None	None	N
L/W	0.802	likely_pathogenic	0.8835	pathogenic	-0.494	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	N
L/Y	0.8204	likely_pathogenic	0.8845	pathogenic	-0.247	Destabilizing	0.999	D	0.661	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.