TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10032	30319;30320;30321	chr2:178704276;178704275;178704274	chr2:179569003;179569002;179569001
N2AB	9715	29368;29369;29370	chr2:178704276;178704275;178704274	chr2:179569003;179569002;179569001
N2A	8788	26587;26588;26589	chr2:178704276;178704275;178704274	chr2:179569003;179569002;179569001
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Ig-85
• Domain position: 44
• Structural Position: 111
• Q(SASA): 0.4237
• 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
G/D	None	None	0.013	None	0.284	0.118	0.0846915920261	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
G/R	rs1336921459	None	0.928	None	0.554	0.25	0.307332253619	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
G/A	0.5126	ambiguous	0.35	ambiguous	-0.178	Destabilizing	0.477	N	0.407	neutral	None	None	None	None	N
G/C	0.8179	likely_pathogenic	0.7022	pathogenic	-0.793	Destabilizing	0.993	D	0.664	neutral	None	None	None	None	N
G/D	0.6385	likely_pathogenic	0.4061	ambiguous	-0.84	Destabilizing	0.013	N	0.284	neutral	None	None	None	None	N
G/E	0.6658	likely_pathogenic	0.4405	ambiguous	-1.005	Destabilizing	0.809	D	0.479	neutral	None	None	None	None	N
G/F	0.9279	likely_pathogenic	0.8685	pathogenic	-0.998	Destabilizing	0.995	D	0.633	neutral	None	None	None	None	N
G/H	0.8633	likely_pathogenic	0.7579	pathogenic	-0.377	Destabilizing	0.995	D	0.563	neutral	None	None	None	None	N
G/I	0.8251	likely_pathogenic	0.7121	pathogenic	-0.409	Destabilizing	0.945	D	0.647	neutral	None	None	None	None	N
G/K	0.8778	likely_pathogenic	0.7548	pathogenic	-0.791	Destabilizing	0.894	D	0.525	neutral	None	None	None	None	N
G/L	0.8785	likely_pathogenic	0.7844	pathogenic	-0.409	Destabilizing	0.894	D	0.658	neutral	None	None	None	None	N
G/M	0.9032	likely_pathogenic	0.8267	pathogenic	-0.55	Destabilizing	0.995	D	0.655	neutral	None	None	None	None	N
G/N	0.6907	likely_pathogenic	0.5273	ambiguous	-0.37	Destabilizing	0.809	D	0.403	neutral	None	None	None	None	N
G/P	0.9619	likely_pathogenic	0.9271	pathogenic	-0.304	Destabilizing	0.017	N	0.354	neutral	None	None	None	None	N
G/Q	0.8005	likely_pathogenic	0.6656	pathogenic	-0.677	Destabilizing	0.894	D	0.56	neutral	None	None	None	None	N
G/R	0.8073	likely_pathogenic	0.6516	pathogenic	-0.32	Destabilizing	0.928	D	0.554	neutral	None	None	None	None	N
G/S	0.3451	ambiguous	0.2426	benign	-0.442	Destabilizing	0.066	N	0.262	neutral	None	None	None	None	N
G/T	0.6809	likely_pathogenic	0.5397	ambiguous	-0.555	Destabilizing	0.809	D	0.499	neutral	None	None	None	None	N
G/V	0.7194	likely_pathogenic	0.5706	pathogenic	-0.304	Destabilizing	0.864	D	0.655	neutral	None	None	None	None	N
G/W	0.8404	likely_pathogenic	0.7471	pathogenic	-1.139	Destabilizing	0.995	D	0.63	neutral	None	None	None	None	N
G/Y	0.8525	likely_pathogenic	0.7486	pathogenic	-0.806	Destabilizing	0.995	D	0.632	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.