TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22044	66355;66356;66357	chr2:178582326;178582325;178582324	chr2:179447053;179447052;179447051
N2AB	20403	61432;61433;61434	chr2:178582326;178582325;178582324	chr2:179447053;179447052;179447051
N2A	19476	58651;58652;58653	chr2:178582326;178582325;178582324	chr2:179447053;179447052;179447051
N2B	12979	39160;39161;39162	chr2:178582326;178582325;178582324	chr2:179447053;179447052;179447051
Novex-1	13104	39535;39536;39537	chr2:178582326;178582325;178582324	chr2:179447053;179447052;179447051
Novex-2	13171	39736;39737;39738	chr2:178582326;178582325;178582324	chr2:179447053;179447052;179447051
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: Fn3-47
• Domain position: 89
• Structural Position: 123
• Q(SASA): 0.2136
• 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/I	rs1490431835	None	0.518	N	0.703	0.376	0.354396617058	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
T/P	None	None	0.938	N	0.651	0.205	0.370240404367	gnomAD-4.0.0	1.62513E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.90877E-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	0.3115	likely_benign	0.3869	ambiguous	-0.771	Destabilizing	0.028	N	0.375	neutral	N	0.519839531	None	None	N
T/C	0.6933	likely_pathogenic	0.7399	pathogenic	-0.402	Destabilizing	0.996	D	0.641	neutral	None	None	None	None	N
T/D	0.9719	likely_pathogenic	0.9605	pathogenic	-0.85	Destabilizing	0.909	D	0.68	prob.neutral	None	None	None	None	N
T/E	0.9733	likely_pathogenic	0.9684	pathogenic	-0.637	Destabilizing	0.74	D	0.671	prob.neutral	None	None	None	None	N
T/F	0.9462	likely_pathogenic	0.956	pathogenic	-0.47	Destabilizing	0.953	D	0.673	prob.neutral	None	None	None	None	N
T/G	0.6735	likely_pathogenic	0.6551	pathogenic	-1.194	Destabilizing	0.587	D	0.699	prob.delet.	None	None	None	None	N
T/H	0.9416	likely_pathogenic	0.9272	pathogenic	-1.222	Destabilizing	0.996	D	0.691	prob.delet.	None	None	None	None	N
T/I	0.8244	likely_pathogenic	0.8914	pathogenic	0.337	Stabilizing	0.518	D	0.703	prob.delet.	N	0.509238535	None	None	N
T/K	0.9757	likely_pathogenic	0.9728	pathogenic	-0.061	Destabilizing	0.909	D	0.67	prob.neutral	None	None	None	None	N
T/L	0.4968	ambiguous	0.5878	pathogenic	0.337	Stabilizing	0.587	D	0.674	prob.neutral	None	None	None	None	N
T/M	0.3989	ambiguous	0.4775	ambiguous	0.132	Stabilizing	0.987	D	0.636	neutral	None	None	None	None	N
T/N	0.812	likely_pathogenic	0.7924	pathogenic	-0.781	Destabilizing	0.883	D	0.64	neutral	N	0.495327568	None	None	N
T/P	0.9075	likely_pathogenic	0.882	pathogenic	-0.001	Destabilizing	0.938	D	0.651	prob.neutral	N	0.484804237	None	None	N
T/Q	0.9402	likely_pathogenic	0.9367	pathogenic	-0.506	Destabilizing	0.909	D	0.664	prob.neutral	None	None	None	None	N
T/R	0.9656	likely_pathogenic	0.9621	pathogenic	-0.351	Destabilizing	0.909	D	0.64	neutral	None	None	None	None	N
T/S	0.2028	likely_benign	0.1864	benign	-1.045	Destabilizing	0.028	N	0.455	neutral	N	0.399894697	None	None	N
T/V	0.624	likely_pathogenic	0.7379	pathogenic	-0.001	Destabilizing	0.037	N	0.465	neutral	None	None	None	None	N
T/W	0.989	likely_pathogenic	0.9877	pathogenic	-0.648	Destabilizing	0.996	D	0.723	deleterious	None	None	None	None	N
T/Y	0.9709	likely_pathogenic	0.9717	pathogenic	-0.198	Destabilizing	0.984	D	0.658	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.