TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20782	62569;62570;62571	chr2:178589381;178589380;178589379	chr2:179454108;179454107;179454106
N2AB	19141	57646;57647;57648	chr2:178589381;178589380;178589379	chr2:179454108;179454107;179454106
N2A	18214	54865;54866;54867	chr2:178589381;178589380;178589379	chr2:179454108;179454107;179454106
N2B	11717	35374;35375;35376	chr2:178589381;178589380;178589379	chr2:179454108;179454107;179454106
Novex-1	11842	35749;35750;35751	chr2:178589381;178589380;178589379	chr2:179454108;179454107;179454106
Novex-2	11909	35950;35951;35952	chr2:178589381;178589380;178589379	chr2:179454108;179454107;179454106
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-122
• Domain position: 14
• Structural Position: 18
• Q(SASA): 0.3935
• Predicted PPI site: I

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/E	None	None	0.477	N	0.583	0.302	0.340032825777	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/T	rs750969532	0.003	0.864	N	0.558	0.426	0.391000631824	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
K/T	rs750969532	0.003	0.864	N	0.558	0.426	0.391000631824	gnomAD-4.0.0	1.59199E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85922E-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	0.7265	likely_pathogenic	0.7321	pathogenic	-0.051	Destabilizing	0.707	D	0.591	neutral	None	None	None	None	I
K/C	0.8697	likely_pathogenic	0.8703	pathogenic	-0.356	Destabilizing	0.995	D	0.71	prob.delet.	None	None	None	None	I
K/D	0.9245	likely_pathogenic	0.9341	pathogenic	0.071	Stabilizing	0.894	D	0.579	neutral	None	None	None	None	I
K/E	0.6167	likely_pathogenic	0.6467	pathogenic	0.102	Stabilizing	0.477	N	0.583	neutral	N	0.51181748	None	None	I
K/F	0.9119	likely_pathogenic	0.9178	pathogenic	-0.146	Destabilizing	0.985	D	0.666	neutral	None	None	None	None	I
K/G	0.8479	likely_pathogenic	0.8437	pathogenic	-0.281	Destabilizing	0.894	D	0.565	neutral	None	None	None	None	I
K/H	0.4818	ambiguous	0.486	ambiguous	-0.471	Destabilizing	0.985	D	0.574	neutral	None	None	None	None	I
K/I	0.72	likely_pathogenic	0.7557	pathogenic	0.485	Stabilizing	0.928	D	0.677	prob.neutral	N	0.51734073	None	None	I
K/L	0.6077	likely_pathogenic	0.6338	pathogenic	0.485	Stabilizing	0.894	D	0.565	neutral	None	None	None	None	I
K/M	0.511	ambiguous	0.5646	pathogenic	0.159	Stabilizing	0.995	D	0.579	neutral	None	None	None	None	I
K/N	0.8192	likely_pathogenic	0.8435	pathogenic	0.014	Stabilizing	0.864	D	0.578	neutral	N	0.513145632	None	None	I
K/P	0.8281	likely_pathogenic	0.8024	pathogenic	0.335	Stabilizing	0.945	D	0.562	neutral	None	None	None	None	I
K/Q	0.291	likely_benign	0.2991	benign	-0.106	Destabilizing	0.864	D	0.578	neutral	N	0.503659357	None	None	I
K/R	0.0866	likely_benign	0.081	benign	-0.128	Destabilizing	0.006	N	0.333	neutral	N	0.428046877	None	None	I
K/S	0.821	likely_pathogenic	0.8383	pathogenic	-0.488	Destabilizing	0.707	D	0.59	neutral	None	None	None	None	I
K/T	0.5213	ambiguous	0.5565	ambiguous	-0.296	Destabilizing	0.864	D	0.558	neutral	N	0.497618819	None	None	I
K/V	0.6383	likely_pathogenic	0.675	pathogenic	0.335	Stabilizing	0.894	D	0.626	neutral	None	None	None	None	I
K/W	0.8966	likely_pathogenic	0.8849	pathogenic	-0.154	Destabilizing	0.995	D	0.714	prob.delet.	None	None	None	None	I
K/Y	0.8359	likely_pathogenic	0.8451	pathogenic	0.187	Stabilizing	0.945	D	0.643	neutral	None	None	None	None	I

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.