TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14683	44272;44273;44274	chr2:178630911;178630910;178630909	chr2:179495638;179495637;179495636
N2AB	13042	39349;39350;39351	chr2:178630911;178630910;178630909	chr2:179495638;179495637;179495636
N2A	12115	36568;36569;36570	chr2:178630911;178630910;178630909	chr2:179495638;179495637;179495636
N2B	5618	17077;17078;17079	chr2:178630911;178630910;178630909	chr2:179495638;179495637;179495636
Novex-1	5743	17452;17453;17454	chr2:178630911;178630910;178630909	chr2:179495638;179495637;179495636
Novex-2	5810	17653;17654;17655	chr2:178630911;178630910;178630909	chr2:179495638;179495637;179495636
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-98
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3869
• 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
S/G	None	None	0.997	N	0.639	0.296	0.126345400529	gnomAD-4.0.0	1.59433E-06	None	None	None	None	N	None	0	0	None	0	2.7835E-05	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
S/A	0.2402	likely_benign	0.2044	benign	-0.352	Destabilizing	0.995	D	0.535	neutral	None	None	None	None	N
S/C	0.5273	ambiguous	0.3805	ambiguous	-0.391	Destabilizing	1.0	D	0.801	deleterious	N	0.483360161	None	None	N
S/D	0.768	likely_pathogenic	0.5799	pathogenic	0.2	Stabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
S/E	0.9424	likely_pathogenic	0.8737	pathogenic	0.171	Stabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
S/F	0.8169	likely_pathogenic	0.7015	pathogenic	-0.798	Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	N
S/G	0.3036	likely_benign	0.202	benign	-0.532	Destabilizing	0.997	D	0.639	neutral	N	0.424006151	None	None	N
S/H	0.8609	likely_pathogenic	0.7685	pathogenic	-0.876	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
S/I	0.819	likely_pathogenic	0.6961	pathogenic	0.003	Stabilizing	0.999	D	0.801	deleterious	N	0.482561193	None	None	N
S/K	0.9903	likely_pathogenic	0.9726	pathogenic	-0.407	Destabilizing	0.998	D	0.749	deleterious	None	None	None	None	N
S/L	0.5276	ambiguous	0.3962	ambiguous	0.003	Stabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
S/M	0.7189	likely_pathogenic	0.6188	pathogenic	-0.105	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
S/N	0.4684	ambiguous	0.3388	benign	-0.342	Destabilizing	0.997	D	0.75	deleterious	N	0.434852044	None	None	N
S/P	0.5185	ambiguous	0.3765	ambiguous	-0.083	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
S/Q	0.9448	likely_pathogenic	0.9027	pathogenic	-0.426	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
S/R	0.9811	likely_pathogenic	0.9485	pathogenic	-0.27	Destabilizing	0.999	D	0.835	deleterious	N	0.480202762	None	None	N
S/T	0.2743	likely_benign	0.2171	benign	-0.352	Destabilizing	0.997	D	0.661	prob.neutral	N	0.478326357	None	None	N
S/V	0.7866	likely_pathogenic	0.6779	pathogenic	-0.083	Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
S/W	0.869	likely_pathogenic	0.7634	pathogenic	-0.88	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
S/Y	0.7525	likely_pathogenic	0.5987	pathogenic	-0.547	Destabilizing	0.999	D	0.823	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.