TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1499	4720;4721;4722	chr2:178777570;178777569;178777568	chr2:179642297;179642296;179642295
N2AB	1499	4720;4721;4722	chr2:178777570;178777569;178777568	chr2:179642297;179642296;179642295
N2A	1499	4720;4721;4722	chr2:178777570;178777569;178777568	chr2:179642297;179642296;179642295
N2B	1453	4582;4583;4584	chr2:178777570;178777569;178777568	chr2:179642297;179642296;179642295
Novex-1	1453	4582;4583;4584	chr2:178777570;178777569;178777568	chr2:179642297;179642296;179642295
Novex-2	1453	4582;4583;4584	chr2:178777570;178777569;178777568	chr2:179642297;179642296;179642295
Novex-3	1499	4720;4721;4722	chr2:178777570;178777569;178777568	chr2:179642297;179642296;179642295

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-6
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.5324
• 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
N/S	rs745448931	0.038	0.905	N	0.292	0.19	0.208816687407	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/S	rs745448931	0.038	0.905	N	0.292	0.19	0.208816687407	gnomAD-4.0.0	2.0525E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79871E-06	1.1595E-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
N/A	0.5084	ambiguous	0.5706	pathogenic	-0.34	Destabilizing	0.994	D	0.489	neutral	None	None	None	None	N
N/C	0.6679	likely_pathogenic	0.7052	pathogenic	0.37	Stabilizing	1.0	D	0.657	neutral	None	None	None	None	N
N/D	0.3269	likely_benign	0.3828	ambiguous	0.081	Stabilizing	0.996	D	0.423	neutral	N	0.482123626	None	None	N
N/E	0.7429	likely_pathogenic	0.7916	pathogenic	0.061	Stabilizing	0.997	D	0.475	neutral	None	None	None	None	N
N/F	0.9217	likely_pathogenic	0.9376	pathogenic	-0.616	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
N/G	0.5071	ambiguous	0.5598	ambiguous	-0.542	Destabilizing	0.997	D	0.412	neutral	None	None	None	None	N
N/H	0.3013	likely_benign	0.3336	benign	-0.593	Destabilizing	1.0	D	0.572	neutral	N	0.509008629	None	None	N
N/I	0.7287	likely_pathogenic	0.7877	pathogenic	0.11	Stabilizing	0.999	D	0.697	prob.neutral	N	0.511834002	None	None	N
N/K	0.8093	likely_pathogenic	0.8526	pathogenic	0.011	Stabilizing	0.996	D	0.479	neutral	N	0.507699608	None	None	N
N/L	0.6125	likely_pathogenic	0.664	pathogenic	0.11	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	N
N/M	0.7353	likely_pathogenic	0.7784	pathogenic	0.446	Stabilizing	1.0	D	0.607	neutral	None	None	None	None	N
N/P	0.6478	likely_pathogenic	0.6811	pathogenic	-0.012	Destabilizing	1.0	D	0.635	neutral	None	None	None	None	N
N/Q	0.7047	likely_pathogenic	0.7445	pathogenic	-0.41	Destabilizing	1.0	D	0.575	neutral	None	None	None	None	N
N/R	0.8024	likely_pathogenic	0.8376	pathogenic	0.016	Stabilizing	1.0	D	0.581	neutral	None	None	None	None	N
N/S	0.1075	likely_benign	0.1196	benign	-0.209	Destabilizing	0.905	D	0.292	neutral	N	0.44281406	None	None	N
N/T	0.325	likely_benign	0.3785	ambiguous	-0.08	Destabilizing	0.992	D	0.456	neutral	N	0.500389753	None	None	N
N/V	0.7172	likely_pathogenic	0.7664	pathogenic	-0.012	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
N/W	0.9584	likely_pathogenic	0.9652	pathogenic	-0.587	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
N/Y	0.5365	ambiguous	0.5862	pathogenic	-0.334	Destabilizing	1.0	D	0.639	neutral	D	0.550364197	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.