TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31642	95149;95150;95151	chr2:178546407;178546406;178546405	chr2:179411134;179411133;179411132
N2AB	30001	90226;90227;90228	chr2:178546407;178546406;178546405	chr2:179411134;179411133;179411132
N2A	29074	87445;87446;87447	chr2:178546407;178546406;178546405	chr2:179411134;179411133;179411132
N2B	22577	67954;67955;67956	chr2:178546407;178546406;178546405	chr2:179411134;179411133;179411132
Novex-1	22702	68329;68330;68331	chr2:178546407;178546406;178546405	chr2:179411134;179411133;179411132
Novex-2	22769	68530;68531;68532	chr2:178546407;178546406;178546405	chr2:179411134;179411133;179411132
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-152
• Domain position: 22
• Structural Position: 41
• Q(SASA): 0.9296
• 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/R	None	None	0.999	N	0.652	0.335	0.399449838166	gnomAD-4.0.0	1.36843E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99489E-07	1.15937E-05	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	0.9346	likely_pathogenic	0.9452	pathogenic	-0.042	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	I
K/C	0.9222	likely_pathogenic	0.927	pathogenic	-0.543	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
K/D	0.9904	likely_pathogenic	0.9913	pathogenic	-0.408	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
K/E	0.8818	likely_pathogenic	0.901	pathogenic	-0.428	Destabilizing	0.999	D	0.727	prob.delet.	N	0.467410555	None	None	I
K/F	0.957	likely_pathogenic	0.9596	pathogenic	-0.427	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
K/G	0.9688	likely_pathogenic	0.9749	pathogenic	-0.14	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
K/H	0.6893	likely_pathogenic	0.6787	pathogenic	-0.194	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
K/I	0.734	likely_pathogenic	0.7682	pathogenic	0.136	Stabilizing	1.0	D	0.738	prob.delet.	N	0.510702759	None	None	I
K/L	0.7697	likely_pathogenic	0.8106	pathogenic	0.136	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
K/M	0.6372	likely_pathogenic	0.6869	pathogenic	-0.23	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
K/N	0.9484	likely_pathogenic	0.9568	pathogenic	-0.083	Destabilizing	1.0	D	0.768	deleterious	N	0.472683089	None	None	I
K/P	0.996	likely_pathogenic	0.9964	pathogenic	0.098	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	I
K/Q	0.5195	ambiguous	0.5544	ambiguous	-0.219	Destabilizing	1.0	D	0.763	deleterious	N	0.515049787	None	None	I
K/R	0.1358	likely_benign	0.1397	benign	-0.171	Destabilizing	0.999	D	0.652	neutral	N	0.41519501	None	None	I
K/S	0.9449	likely_pathogenic	0.9544	pathogenic	-0.414	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	I
K/T	0.78	likely_pathogenic	0.8113	pathogenic	-0.333	Destabilizing	1.0	D	0.709	prob.delet.	N	0.500619052	None	None	I
K/V	0.7316	likely_pathogenic	0.7668	pathogenic	0.098	Stabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
K/W	0.9612	likely_pathogenic	0.9589	pathogenic	-0.549	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	I
K/Y	0.9071	likely_pathogenic	0.9049	pathogenic	-0.208	Destabilizing	1.0	D	0.743	deleterious	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.