TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28945	87058;87059;87060	chr2:178558626;178558625;178558624	chr2:179423353;179423352;179423351
N2AB	27304	82135;82136;82137	chr2:178558626;178558625;178558624	chr2:179423353;179423352;179423351
N2A	26377	79354;79355;79356	chr2:178558626;178558625;178558624	chr2:179423353;179423352;179423351
N2B	19880	59863;59864;59865	chr2:178558626;178558625;178558624	chr2:179423353;179423352;179423351
Novex-1	20005	60238;60239;60240	chr2:178558626;178558625;178558624	chr2:179423353;179423352;179423351
Novex-2	20072	60439;60440;60441	chr2:178558626;178558625;178558624	chr2:179423353;179423352;179423351
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-99
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.1874
• 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
P/L	None	None	1.0	N	0.905	0.463	0.705626407511	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
P/T	None	None	1.0	N	0.846	0.382	0.480198768302	gnomAD-4.0.0	1.5995E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.90498E-05	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
P/A	0.0859	likely_benign	0.0775	benign	-1.621	Destabilizing	1.0	D	0.851	deleterious	N	0.457774273	None	None	N
P/C	0.5161	ambiguous	0.4344	ambiguous	-1.249	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/D	0.9153	likely_pathogenic	0.8815	pathogenic	-2.55	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
P/E	0.6482	likely_pathogenic	0.5813	pathogenic	-2.555	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/F	0.6861	likely_pathogenic	0.5755	pathogenic	-1.355	Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
P/G	0.5983	likely_pathogenic	0.5263	ambiguous	-1.914	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/H	0.4464	ambiguous	0.3776	ambiguous	-1.409	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
P/I	0.3701	ambiguous	0.2925	benign	-0.895	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
P/K	0.6021	likely_pathogenic	0.5241	ambiguous	-1.339	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
P/L	0.2142	likely_benign	0.167	benign	-0.895	Destabilizing	1.0	D	0.905	deleterious	N	0.514101889	None	None	N
P/M	0.4368	ambiguous	0.3395	benign	-0.681	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
P/N	0.7556	likely_pathogenic	0.6591	pathogenic	-1.295	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
P/Q	0.3276	likely_benign	0.2587	benign	-1.548	Destabilizing	1.0	D	0.854	deleterious	N	0.498337811	None	None	N
P/R	0.4111	ambiguous	0.3451	ambiguous	-0.758	Destabilizing	1.0	D	0.91	deleterious	N	0.501478136	None	None	N
P/S	0.214	likely_benign	0.1735	benign	-1.657	Destabilizing	1.0	D	0.855	deleterious	N	0.471586275	None	None	N
P/T	0.2353	likely_benign	0.189	benign	-1.573	Destabilizing	1.0	D	0.846	deleterious	N	0.499605258	None	None	N
P/V	0.2283	likely_benign	0.1856	benign	-1.107	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
P/W	0.874	likely_pathogenic	0.8237	pathogenic	-1.588	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/Y	0.7243	likely_pathogenic	0.6323	pathogenic	-1.303	Destabilizing	1.0	D	0.92	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.