TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22685	68278;68279;68280	chr2:178578977;178578976;178578975	chr2:179443704;179443703;179443702
N2AB	21044	63355;63356;63357	chr2:178578977;178578976;178578975	chr2:179443704;179443703;179443702
N2A	20117	60574;60575;60576	chr2:178578977;178578976;178578975	chr2:179443704;179443703;179443702
N2B	13620	41083;41084;41085	chr2:178578977;178578976;178578975	chr2:179443704;179443703;179443702
Novex-1	13745	41458;41459;41460	chr2:178578977;178578976;178578975	chr2:179443704;179443703;179443702
Novex-2	13812	41659;41660;41661	chr2:178578977;178578976;178578975	chr2:179443704;179443703;179443702
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-52
• Domain position: 43
• Structural Position: 44
• Q(SASA): 0.3078
• 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
D/N	rs866478447	None	0.684	N	0.383	0.252	0.32082282376	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
D/N	rs866478447	None	0.684	N	0.383	0.252	0.32082282376	gnomAD-4.0.0	6.57999E-06	None	None	None	None	N	None	2.41534E-05	0	None	0	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
D/A	0.7817	likely_pathogenic	0.7074	pathogenic	-0.302	Destabilizing	0.684	D	0.456	neutral	N	0.521943181	None	None	N
D/C	0.8833	likely_pathogenic	0.8715	pathogenic	-0.325	Destabilizing	0.996	D	0.535	neutral	None	None	None	None	N
D/E	0.5726	likely_pathogenic	0.495	ambiguous	-0.866	Destabilizing	0.007	N	0.107	neutral	N	0.437169714	None	None	N
D/F	0.9652	likely_pathogenic	0.9452	pathogenic	-0.554	Destabilizing	0.953	D	0.511	neutral	None	None	None	None	N
D/G	0.7718	likely_pathogenic	0.6754	pathogenic	-0.643	Destabilizing	0.684	D	0.387	neutral	D	0.524522127	None	None	N
D/H	0.8419	likely_pathogenic	0.7942	pathogenic	-1.042	Destabilizing	0.015	N	0.267	neutral	N	0.485118173	None	None	N
D/I	0.9306	likely_pathogenic	0.9095	pathogenic	0.591	Stabilizing	0.953	D	0.526	neutral	None	None	None	None	N
D/K	0.9599	likely_pathogenic	0.9368	pathogenic	-0.741	Destabilizing	0.59	D	0.412	neutral	None	None	None	None	N
D/L	0.9132	likely_pathogenic	0.8826	pathogenic	0.591	Stabilizing	0.742	D	0.487	neutral	None	None	None	None	N
D/M	0.9616	likely_pathogenic	0.9444	pathogenic	1.081	Stabilizing	0.996	D	0.49	neutral	None	None	None	None	N
D/N	0.4318	ambiguous	0.3364	benign	-0.985	Destabilizing	0.684	D	0.383	neutral	N	0.516825363	None	None	N
D/P	0.9905	likely_pathogenic	0.9843	pathogenic	0.32	Stabilizing	0.953	D	0.391	neutral	None	None	None	None	N
D/Q	0.8966	likely_pathogenic	0.8518	pathogenic	-0.778	Destabilizing	0.59	D	0.367	neutral	None	None	None	None	N
D/R	0.9569	likely_pathogenic	0.9369	pathogenic	-0.855	Destabilizing	0.009	N	0.249	neutral	None	None	None	None	N
D/S	0.594	likely_pathogenic	0.4988	ambiguous	-1.335	Destabilizing	0.742	D	0.354	neutral	None	None	None	None	N
D/T	0.8571	likely_pathogenic	0.7948	pathogenic	-1.043	Destabilizing	0.742	D	0.371	neutral	None	None	None	None	N
D/V	0.8195	likely_pathogenic	0.7812	pathogenic	0.32	Stabilizing	0.939	D	0.49	neutral	N	0.468495176	None	None	N
D/W	0.9916	likely_pathogenic	0.988	pathogenic	-0.766	Destabilizing	0.996	D	0.599	neutral	None	None	None	None	N
D/Y	0.783	likely_pathogenic	0.727	pathogenic	-0.426	Destabilizing	0.884	D	0.532	neutral	N	0.509009326	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.