TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31661	95206;95207;95208	chr2:178546350;178546349;178546348	chr2:179411077;179411076;179411075
N2AB	30020	90283;90284;90285	chr2:178546350;178546349;178546348	chr2:179411077;179411076;179411075
N2A	29093	87502;87503;87504	chr2:178546350;178546349;178546348	chr2:179411077;179411076;179411075
N2B	22596	68011;68012;68013	chr2:178546350;178546349;178546348	chr2:179411077;179411076;179411075
Novex-1	22721	68386;68387;68388	chr2:178546350;178546349;178546348	chr2:179411077;179411076;179411075
Novex-2	22788	68587;68588;68589	chr2:178546350;178546349;178546348	chr2:179411077;179411076;179411075
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-152
• Domain position: 41
• Structural Position: 115
• Q(SASA): 0.6596
• 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
K/E	rs1268995899	0.295	0.999	N	0.566	0.372	0.215869574891	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/E	rs1268995899	0.295	0.999	N	0.566	0.372	0.215869574891	gnomAD-4.0.0	1.36841E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99476E-07	1.15934E-05	0
K/N	None	None	1.0	N	0.657	0.253	0.137902524267	gnomAD-4.0.0	6.84208E-07	None	None	None	None	N	None	0	0	None	3.82673E-05	0	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
K/A	0.7635	likely_pathogenic	0.7898	pathogenic	-0.372	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
K/C	0.9329	likely_pathogenic	0.9368	pathogenic	-0.344	Destabilizing	1.0	D	0.622	neutral	None	None	None	None	N
K/D	0.7844	likely_pathogenic	0.8149	pathogenic	-0.018	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
K/E	0.5798	likely_pathogenic	0.6063	pathogenic	0.079	Stabilizing	0.999	D	0.566	neutral	N	0.506253292	None	None	N
K/F	0.9626	likely_pathogenic	0.9679	pathogenic	-0.086	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
K/G	0.7723	likely_pathogenic	0.7853	pathogenic	-0.726	Destabilizing	1.0	D	0.603	neutral	None	None	None	None	N
K/H	0.5329	ambiguous	0.558	ambiguous	-1.104	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	N
K/I	0.7953	likely_pathogenic	0.824	pathogenic	0.534	Stabilizing	1.0	D	0.622	neutral	N	0.515219492	None	None	N
K/L	0.7481	likely_pathogenic	0.7811	pathogenic	0.534	Stabilizing	1.0	D	0.603	neutral	None	None	None	None	N
K/M	0.5733	likely_pathogenic	0.6151	pathogenic	0.355	Stabilizing	1.0	D	0.592	neutral	None	None	None	None	N
K/N	0.6502	likely_pathogenic	0.6891	pathogenic	-0.292	Destabilizing	1.0	D	0.657	neutral	N	0.505733217	None	None	N
K/P	0.9438	likely_pathogenic	0.95	pathogenic	0.263	Stabilizing	1.0	D	0.623	neutral	None	None	None	None	N
K/Q	0.4027	ambiguous	0.4272	ambiguous	-0.335	Destabilizing	1.0	D	0.647	neutral	N	0.464138812	None	None	N
K/R	0.1166	likely_benign	0.118	benign	-0.579	Destabilizing	0.999	D	0.546	neutral	N	0.387055033	None	None	N
K/S	0.7952	likely_pathogenic	0.8149	pathogenic	-0.877	Destabilizing	0.999	D	0.621	neutral	None	None	None	None	N
K/T	0.4718	ambiguous	0.512	ambiguous	-0.579	Destabilizing	1.0	D	0.657	neutral	N	0.508677522	None	None	N
K/V	0.7458	likely_pathogenic	0.7808	pathogenic	0.263	Stabilizing	1.0	D	0.595	neutral	None	None	None	None	N
K/W	0.9395	likely_pathogenic	0.9452	pathogenic	-0.016	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	N
K/Y	0.8462	likely_pathogenic	0.8524	pathogenic	0.27	Stabilizing	1.0	D	0.566	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.