TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14182	42769;42770;42771	chr2:178633955;178633954;178633953	chr2:179498682;179498681;179498680
N2AB	12541	37846;37847;37848	chr2:178633955;178633954;178633953	chr2:179498682;179498681;179498680
N2A	11614	35065;35066;35067	chr2:178633955;178633954;178633953	chr2:179498682;179498681;179498680
N2B	5117	15574;15575;15576	chr2:178633955;178633954;178633953	chr2:179498682;179498681;179498680
Novex-1	5242	15949;15950;15951	chr2:178633955;178633954;178633953	chr2:179498682;179498681;179498680
Novex-2	5309	16150;16151;16152	chr2:178633955;178633954;178633953	chr2:179498682;179498681;179498680
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-92
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.701
• 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
H/P	rs794729428	None	0.999	N	0.564	0.472	0.573614764001	gnomAD-4.0.0	2.05301E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69886E-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
H/A	0.498	ambiguous	0.6452	pathogenic	0.211	Stabilizing	0.993	D	0.517	neutral	None	None	None	None	N
H/C	0.3894	ambiguous	0.5132	ambiguous	0.32	Stabilizing	1.0	D	0.645	neutral	None	None	None	None	N
H/D	0.4591	ambiguous	0.6333	pathogenic	-0.269	Destabilizing	0.961	D	0.533	neutral	N	0.508614036	None	None	N
H/E	0.5299	ambiguous	0.7086	pathogenic	-0.253	Destabilizing	0.985	D	0.495	neutral	None	None	None	None	N
H/F	0.4118	ambiguous	0.4708	ambiguous	0.834	Stabilizing	0.999	D	0.531	neutral	None	None	None	None	N
H/G	0.5155	ambiguous	0.6697	pathogenic	-0.018	Destabilizing	0.985	D	0.521	neutral	None	None	None	None	N
H/I	0.5101	ambiguous	0.6341	pathogenic	0.784	Stabilizing	0.999	D	0.609	neutral	None	None	None	None	N
H/K	0.4055	ambiguous	0.5744	pathogenic	0.09	Stabilizing	0.985	D	0.518	neutral	None	None	None	None	N
H/L	0.2373	likely_benign	0.2945	benign	0.784	Stabilizing	0.997	D	0.553	neutral	N	0.509125856	None	None	N
H/M	0.6352	likely_pathogenic	0.7322	pathogenic	0.436	Stabilizing	1.0	D	0.568	neutral	None	None	None	None	N
H/N	0.1908	likely_benign	0.2621	benign	-0.11	Destabilizing	0.4	N	0.227	neutral	N	0.493813693	None	None	N
H/P	0.2405	likely_benign	0.3132	benign	0.615	Stabilizing	0.999	D	0.564	neutral	N	0.509125856	None	None	N
H/Q	0.3128	likely_benign	0.4369	ambiguous	-0.013	Destabilizing	0.997	D	0.494	neutral	N	0.489021949	None	None	N
H/R	0.1925	likely_benign	0.2952	benign	-0.368	Destabilizing	0.997	D	0.47	neutral	N	0.489982371	None	None	N
H/S	0.3835	ambiguous	0.5144	ambiguous	-0.016	Destabilizing	0.985	D	0.526	neutral	None	None	None	None	N
H/T	0.4974	ambiguous	0.6534	pathogenic	0.097	Stabilizing	0.996	D	0.483	neutral	None	None	None	None	N
H/V	0.4407	ambiguous	0.5857	pathogenic	0.615	Stabilizing	0.999	D	0.603	neutral	None	None	None	None	N
H/W	0.4989	ambiguous	0.6213	pathogenic	0.773	Stabilizing	1.0	D	0.629	neutral	None	None	None	None	N
H/Y	0.1553	likely_benign	0.2026	benign	0.987	Stabilizing	0.997	D	0.466	neutral	N	0.511646681	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.