TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21480	64663;64664;64665	chr2:178585306;178585305;178585304	chr2:179450033;179450032;179450031
N2AB	19839	59740;59741;59742	chr2:178585306;178585305;178585304	chr2:179450033;179450032;179450031
N2A	18912	56959;56960;56961	chr2:178585306;178585305;178585304	chr2:179450033;179450032;179450031
N2B	12415	37468;37469;37470	chr2:178585306;178585305;178585304	chr2:179450033;179450032;179450031
Novex-1	12540	37843;37844;37845	chr2:178585306;178585305;178585304	chr2:179450033;179450032;179450031
Novex-2	12607	38044;38045;38046	chr2:178585306;178585305;178585304	chr2:179450033;179450032;179450031
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-124
• Domain position: 12
• Structural Position: 23
• Q(SASA): 0.3917
• 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
A/T	None	None	1.0	N	0.703	0.291	0.225902525712	gnomAD-4.0.0	6.85782E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00774E-07	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
A/C	0.78	likely_pathogenic	0.6705	pathogenic	-0.826	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
A/D	0.9151	likely_pathogenic	0.8355	pathogenic	-0.722	Destabilizing	1.0	D	0.79	deleterious	N	0.457466541	None	None	N
A/E	0.7584	likely_pathogenic	0.6528	pathogenic	-0.808	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
A/F	0.8529	likely_pathogenic	0.7635	pathogenic	-0.895	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
A/G	0.3635	ambiguous	0.2787	benign	-0.839	Destabilizing	1.0	D	0.539	neutral	N	0.487180591	None	None	N
A/H	0.8662	likely_pathogenic	0.8047	pathogenic	-0.884	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
A/I	0.6781	likely_pathogenic	0.522	ambiguous	-0.341	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
A/K	0.8191	likely_pathogenic	0.7311	pathogenic	-1.051	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
A/L	0.6674	likely_pathogenic	0.5369	ambiguous	-0.341	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
A/M	0.6149	likely_pathogenic	0.4818	ambiguous	-0.335	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
A/N	0.7615	likely_pathogenic	0.6422	pathogenic	-0.715	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
A/P	0.9045	likely_pathogenic	0.8001	pathogenic	-0.406	Destabilizing	1.0	D	0.751	deleterious	N	0.470771403	None	None	N
A/Q	0.6708	likely_pathogenic	0.6009	pathogenic	-0.926	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
A/R	0.7497	likely_pathogenic	0.675	pathogenic	-0.613	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
A/S	0.1957	likely_benign	0.1601	benign	-1.027	Destabilizing	1.0	D	0.554	neutral	N	0.49782581	None	None	N
A/T	0.3735	ambiguous	0.2494	benign	-1.021	Destabilizing	1.0	D	0.703	prob.neutral	N	0.452667148	None	None	N
A/V	0.3434	ambiguous	0.2368	benign	-0.406	Destabilizing	1.0	D	0.633	neutral	N	0.497457664	None	None	N
A/W	0.974	likely_pathogenic	0.9511	pathogenic	-1.136	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
A/Y	0.8783	likely_pathogenic	0.7981	pathogenic	-0.77	Destabilizing	1.0	D	0.802	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.