TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30283	91072;91073;91074	chr2:178552053;178552052;178552051	chr2:179416780;179416779;179416778
N2AB	28642	86149;86150;86151	chr2:178552053;178552052;178552051	chr2:179416780;179416779;179416778
N2A	27715	83368;83369;83370	chr2:178552053;178552052;178552051	chr2:179416780;179416779;179416778
N2B	21218	63877;63878;63879	chr2:178552053;178552052;178552051	chr2:179416780;179416779;179416778
Novex-1	21343	64252;64253;64254	chr2:178552053;178552052;178552051	chr2:179416780;179416779;179416778
Novex-2	21410	64453;64454;64455	chr2:178552053;178552052;178552051	chr2:179416780;179416779;179416778
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-108
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.3041
• 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	rs1385680700	None	1.0	D	0.723	0.28	0.408444019923	gnomAD-4.0.0	1.59155E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85863E-06	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	0.1076	likely_benign	0.1117	benign	-1.041	Destabilizing	0.999	D	0.531	neutral	N	0.477093231	None	None	N
T/C	0.4728	ambiguous	0.5095	ambiguous	-0.509	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
T/D	0.7085	likely_pathogenic	0.7467	pathogenic	-0.274	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
T/E	0.584	likely_pathogenic	0.6211	pathogenic	-0.158	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
T/F	0.3895	ambiguous	0.4248	ambiguous	-0.857	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
T/G	0.3493	ambiguous	0.3611	ambiguous	-1.402	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
T/H	0.3824	ambiguous	0.4101	ambiguous	-1.465	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
T/I	0.226	likely_benign	0.2487	benign	-0.128	Destabilizing	1.0	D	0.783	deleterious	N	0.486843374	None	None	N
T/K	0.4371	ambiguous	0.4643	ambiguous	-0.42	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
T/L	0.1601	likely_benign	0.1662	benign	-0.128	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
T/M	0.1197	likely_benign	0.1179	benign	-0.042	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
T/N	0.2034	likely_benign	0.213	benign	-0.712	Destabilizing	1.0	D	0.723	prob.delet.	D	0.5246582	None	None	N
T/P	0.7729	likely_pathogenic	0.7733	pathogenic	-0.399	Destabilizing	1.0	D	0.793	deleterious	N	0.49794619	None	None	N
T/Q	0.3344	likely_benign	0.3533	ambiguous	-0.638	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
T/R	0.3605	ambiguous	0.3904	ambiguous	-0.435	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
T/S	0.1236	likely_benign	0.1244	benign	-1.082	Destabilizing	0.999	D	0.503	neutral	N	0.443885043	None	None	N
T/V	0.1469	likely_benign	0.1625	benign	-0.399	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
T/W	0.797	likely_pathogenic	0.8172	pathogenic	-0.852	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
T/Y	0.4249	ambiguous	0.4739	ambiguous	-0.552	Destabilizing	1.0	D	0.825	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.