TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23416	70471;70472;70473	chr2:178575886;178575885;178575884	chr2:179440613;179440612;179440611
N2AB	21775	65548;65549;65550	chr2:178575886;178575885;178575884	chr2:179440613;179440612;179440611
N2A	20848	62767;62768;62769	chr2:178575886;178575885;178575884	chr2:179440613;179440612;179440611
N2B	14351	43276;43277;43278	chr2:178575886;178575885;178575884	chr2:179440613;179440612;179440611
Novex-1	14476	43651;43652;43653	chr2:178575886;178575885;178575884	chr2:179440613;179440612;179440611
Novex-2	14543	43852;43853;43854	chr2:178575886;178575885;178575884	chr2:179440613;179440612;179440611
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-129
• Domain position: 72
• Structural Position: 157
• Q(SASA): 0.2001
• 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
T/N	rs762398059	-1.352	0.989	N	0.609	0.308	0.486920840936	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
T/N	rs762398059	-1.352	0.989	N	0.609	0.308	0.486920840936	gnomAD-4.0.0	1.59168E-06	None	None	None	None	N	None	0	2.28645E-05	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
T/A	0.1034	likely_benign	0.1072	benign	-0.977	Destabilizing	0.625	D	0.51	neutral	N	0.498899194	None	None	N
T/C	0.3574	ambiguous	0.4049	ambiguous	-0.778	Destabilizing	0.016	N	0.333	neutral	None	None	None	None	N
T/D	0.3816	ambiguous	0.4192	ambiguous	-1.227	Destabilizing	0.991	D	0.637	neutral	None	None	None	None	N
T/E	0.2532	likely_benign	0.2959	benign	-1.129	Destabilizing	0.974	D	0.634	neutral	None	None	None	None	N
T/F	0.3	likely_benign	0.3271	benign	-0.745	Destabilizing	0.949	D	0.677	prob.neutral	None	None	None	None	N
T/G	0.3196	likely_benign	0.3381	benign	-1.329	Destabilizing	0.915	D	0.638	neutral	None	None	None	None	N
T/H	0.2143	likely_benign	0.2399	benign	-1.582	Destabilizing	0.998	D	0.636	neutral	None	None	None	None	N
T/I	0.1739	likely_benign	0.195	benign	-0.096	Destabilizing	0.669	D	0.599	neutral	N	0.485087353	None	None	N
T/K	0.2543	likely_benign	0.2954	benign	-0.882	Destabilizing	0.915	D	0.614	neutral	None	None	None	None	N
T/L	0.1245	likely_benign	0.1356	benign	-0.096	Destabilizing	0.275	N	0.534	neutral	None	None	None	None	N
T/M	0.0847	likely_benign	0.0863	benign	0.101	Stabilizing	0.325	N	0.452	neutral	None	None	None	None	N
T/N	0.1145	likely_benign	0.1117	benign	-1.208	Destabilizing	0.989	D	0.609	neutral	N	0.493721407	None	None	N
T/P	0.9123	likely_pathogenic	0.9212	pathogenic	-0.357	Destabilizing	0.989	D	0.648	neutral	D	0.526918177	None	None	N
T/Q	0.1974	likely_benign	0.2192	benign	-1.22	Destabilizing	0.974	D	0.654	neutral	None	None	None	None	N
T/R	0.2231	likely_benign	0.2612	benign	-0.819	Destabilizing	0.974	D	0.647	neutral	None	None	None	None	N
T/S	0.1147	likely_benign	0.1161	benign	-1.4	Destabilizing	0.891	D	0.562	neutral	N	0.49116374	None	None	N
T/V	0.1307	likely_benign	0.146	benign	-0.357	Destabilizing	0.525	D	0.527	neutral	None	None	None	None	N
T/W	0.6682	likely_pathogenic	0.6962	pathogenic	-0.797	Destabilizing	0.998	D	0.652	neutral	None	None	None	None	N
T/Y	0.3327	likely_benign	0.3552	ambiguous	-0.501	Destabilizing	0.974	D	0.677	prob.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.