TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22646	68161;68162;68163	chr2:178579094;178579093;178579092	chr2:179443821;179443820;179443819
N2AB	21005	63238;63239;63240	chr2:178579094;178579093;178579092	chr2:179443821;179443820;179443819
N2A	20078	60457;60458;60459	chr2:178579094;178579093;178579092	chr2:179443821;179443820;179443819
N2B	13581	40966;40967;40968	chr2:178579094;178579093;178579092	chr2:179443821;179443820;179443819
Novex-1	13706	41341;41342;41343	chr2:178579094;178579093;178579092	chr2:179443821;179443820;179443819
Novex-2	13773	41542;41543;41544	chr2:178579094;178579093;178579092	chr2:179443821;179443820;179443819
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-52
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2242
• 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
I/V	rs1348616703	None	0.985	N	0.375	0.197	0.40749426699	gnomAD-4.0.0	1.59215E-06	None	None	None	None	N	None	0	0	None	0	2.78133E-05	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
I/A	0.4298	ambiguous	0.3936	ambiguous	-1.647	Destabilizing	0.998	D	0.586	neutral	None	None	None	None	N
I/C	0.662	likely_pathogenic	0.6423	pathogenic	-1.024	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
I/D	0.7932	likely_pathogenic	0.7638	pathogenic	-1.04	Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	N
I/E	0.605	likely_pathogenic	0.5853	pathogenic	-1.071	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
I/F	0.2399	likely_benign	0.2181	benign	-1.315	Destabilizing	0.999	D	0.757	deleterious	N	0.496908664	None	None	N
I/G	0.7611	likely_pathogenic	0.7319	pathogenic	-1.927	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
I/H	0.5848	likely_pathogenic	0.5477	ambiguous	-1.109	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
I/K	0.3717	ambiguous	0.326	benign	-1.007	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
I/L	0.1236	likely_benign	0.1208	benign	-0.968	Destabilizing	0.985	D	0.368	neutral	N	0.488230466	None	None	N
I/M	0.1351	likely_benign	0.1252	benign	-0.725	Destabilizing	0.999	D	0.758	deleterious	N	0.489270616	None	None	N
I/N	0.3702	ambiguous	0.3431	ambiguous	-0.78	Destabilizing	0.999	D	0.877	deleterious	N	0.507856376	None	None	N
I/P	0.3976	ambiguous	0.3876	ambiguous	-1.163	Destabilizing	0.999	D	0.881	deleterious	None	None	None	None	N
I/Q	0.4818	ambiguous	0.4446	ambiguous	-1.033	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
I/R	0.3613	ambiguous	0.3188	benign	-0.378	Destabilizing	0.999	D	0.878	deleterious	None	None	None	None	N
I/S	0.3865	ambiguous	0.3583	ambiguous	-1.386	Destabilizing	0.999	D	0.809	deleterious	N	0.444863691	None	None	N
I/T	0.3997	ambiguous	0.3526	ambiguous	-1.307	Destabilizing	0.999	D	0.774	deleterious	N	0.466759115	None	None	N
I/V	0.1034	likely_benign	0.0972	benign	-1.163	Destabilizing	0.985	D	0.375	neutral	N	0.416138294	None	None	N
I/W	0.8484	likely_pathogenic	0.8311	pathogenic	-1.311	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
I/Y	0.5504	ambiguous	0.5354	ambiguous	-1.094	Destabilizing	0.999	D	0.822	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.