TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32082	96469;96470;96471	chr2:178543900;178543899;178543898	chr2:179408627;179408626;179408625
N2AB	30441	91546;91547;91548	chr2:178543900;178543899;178543898	chr2:179408627;179408626;179408625
N2A	29514	88765;88766;88767	chr2:178543900;178543899;178543898	chr2:179408627;179408626;179408625
N2B	23017	69274;69275;69276	chr2:178543900;178543899;178543898	chr2:179408627;179408626;179408625
Novex-1	23142	69649;69650;69651	chr2:178543900;178543899;178543898	chr2:179408627;179408626;179408625
Novex-2	23209	69850;69851;69852	chr2:178543900;178543899;178543898	chr2:179408627;179408626;179408625
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-153
• Domain position: 66
• Structural Position: 153
• Q(SASA): 0.7297
• 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
K/R	rs1388102991	None	0.999	N	0.611	0.364	0.399017061211	gnomAD-4.0.0	4.77426E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.57608E-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
K/A	0.769	likely_pathogenic	0.7366	pathogenic	-0.324	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
K/C	0.809	likely_pathogenic	0.8017	pathogenic	-0.335	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
K/D	0.9286	likely_pathogenic	0.9107	pathogenic	0.235	Stabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/E	0.6153	likely_pathogenic	0.5574	ambiguous	0.31	Stabilizing	0.999	D	0.665	neutral	D	0.533539547	None	None	N
K/F	0.9047	likely_pathogenic	0.8808	pathogenic	-0.163	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/G	0.8861	likely_pathogenic	0.857	pathogenic	-0.638	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
K/H	0.4797	ambiguous	0.4403	ambiguous	-0.945	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
K/I	0.4985	ambiguous	0.4915	ambiguous	0.46	Stabilizing	1.0	D	0.787	deleterious	N	0.487658247	None	None	N
K/L	0.6039	likely_pathogenic	0.5753	pathogenic	0.46	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
K/M	0.4483	ambiguous	0.4127	ambiguous	0.257	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
K/N	0.8121	likely_pathogenic	0.7688	pathogenic	-0.037	Destabilizing	1.0	D	0.755	deleterious	N	0.489797841	None	None	N
K/P	0.9142	likely_pathogenic	0.9137	pathogenic	0.229	Stabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
K/Q	0.3204	likely_benign	0.2868	benign	-0.133	Destabilizing	1.0	D	0.742	deleterious	N	0.494797817	None	None	N
K/R	0.0952	likely_benign	0.0938	benign	-0.325	Destabilizing	0.999	D	0.611	neutral	N	0.513569706	None	None	N
K/S	0.8223	likely_pathogenic	0.7789	pathogenic	-0.673	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
K/T	0.4829	ambiguous	0.4334	ambiguous	-0.406	Destabilizing	1.0	D	0.777	deleterious	D	0.523362625	None	None	N
K/V	0.5052	ambiguous	0.4975	ambiguous	0.229	Stabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
K/W	0.8698	likely_pathogenic	0.8348	pathogenic	-0.067	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/Y	0.7739	likely_pathogenic	0.7369	pathogenic	0.233	Stabilizing	1.0	D	0.759	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.