TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32064	96415;96416;96417	chr2:178543954;178543953;178543952	chr2:179408681;179408680;179408679
N2AB	30423	91492;91493;91494	chr2:178543954;178543953;178543952	chr2:179408681;179408680;179408679
N2A	29496	88711;88712;88713	chr2:178543954;178543953;178543952	chr2:179408681;179408680;179408679
N2B	22999	69220;69221;69222	chr2:178543954;178543953;178543952	chr2:179408681;179408680;179408679
Novex-1	23124	69595;69596;69597	chr2:178543954;178543953;178543952	chr2:179408681;179408680;179408679
Novex-2	23191	69796;69797;69798	chr2:178543954;178543953;178543952	chr2:179408681;179408680;179408679
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: Ig-153
• Domain position: 48
• Structural Position: 130
• Q(SASA): 0.2477
• 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	None	None	1.0	D	0.648	0.365	0.500613528874	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2519	likely_benign	0.2046	benign	-0.745	Destabilizing	0.999	D	0.461	neutral	N	0.499063778	None	None	N
T/C	0.8318	likely_pathogenic	0.7893	pathogenic	-0.299	Destabilizing	1.0	D	0.618	neutral	None	None	None	None	N
T/D	0.7628	likely_pathogenic	0.6875	pathogenic	0.364	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
T/E	0.7911	likely_pathogenic	0.7241	pathogenic	0.313	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	N
T/F	0.8584	likely_pathogenic	0.7921	pathogenic	-1.086	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
T/G	0.4346	ambiguous	0.3822	ambiguous	-0.922	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
T/H	0.6902	likely_pathogenic	0.6162	pathogenic	-1.226	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
T/I	0.8162	likely_pathogenic	0.7504	pathogenic	-0.383	Destabilizing	1.0	D	0.633	neutral	N	0.503787493	None	None	N
T/K	0.6154	likely_pathogenic	0.5346	ambiguous	-0.434	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
T/L	0.4482	ambiguous	0.3534	ambiguous	-0.383	Destabilizing	0.999	D	0.563	neutral	None	None	None	None	N
T/M	0.3052	likely_benign	0.2487	benign	-0.035	Destabilizing	1.0	D	0.621	neutral	None	None	None	None	N
T/N	0.3453	ambiguous	0.2721	benign	-0.21	Destabilizing	1.0	D	0.648	neutral	D	0.529691165	None	None	N
T/P	0.6979	likely_pathogenic	0.6278	pathogenic	-0.474	Destabilizing	1.0	D	0.625	neutral	N	0.502470819	None	None	N
T/Q	0.6176	likely_pathogenic	0.5452	ambiguous	-0.435	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
T/R	0.5708	likely_pathogenic	0.4887	ambiguous	-0.201	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	N
T/S	0.1948	likely_benign	0.1645	benign	-0.539	Destabilizing	0.999	D	0.455	neutral	N	0.477531548	None	None	N
T/V	0.5845	likely_pathogenic	0.51	ambiguous	-0.474	Destabilizing	0.999	D	0.505	neutral	None	None	None	None	N
T/W	0.9561	likely_pathogenic	0.9334	pathogenic	-0.998	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
T/Y	0.87	likely_pathogenic	0.8136	pathogenic	-0.761	Destabilizing	1.0	D	0.711	prob.delet.	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.