TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17951	54076;54077;54078	chr2:178605444;178605443;178605442	chr2:179470171;179470170;179470169
N2AB	16310	49153;49154;49155	chr2:178605444;178605443;178605442	chr2:179470171;179470170;179470169
N2A	15383	46372;46373;46374	chr2:178605444;178605443;178605442	chr2:179470171;179470170;179470169
N2B	8886	26881;26882;26883	chr2:178605444;178605443;178605442	chr2:179470171;179470170;179470169
Novex-1	9011	27256;27257;27258	chr2:178605444;178605443;178605442	chr2:179470171;179470170;179470169
Novex-2	9078	27457;27458;27459	chr2:178605444;178605443;178605442	chr2:179470171;179470170;179470169
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-18
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.4728
• 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
P/R	None	None	0.998	N	0.873	0.397	0.466571191598	gnomAD-4.0.0	1.60174E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87853E-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
P/A	0.1897	likely_benign	0.1619	benign	-1.143	Destabilizing	0.982	D	0.739	deleterious	N	0.443172967	None	None	I
P/C	0.7825	likely_pathogenic	0.7586	pathogenic	-0.785	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	I
P/D	0.9291	likely_pathogenic	0.8948	pathogenic	-0.758	Destabilizing	0.998	D	0.806	deleterious	None	None	None	None	I
P/E	0.8354	likely_pathogenic	0.7828	pathogenic	-0.774	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	I
P/F	0.8578	likely_pathogenic	0.7994	pathogenic	-0.857	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	I
P/G	0.6747	likely_pathogenic	0.6323	pathogenic	-1.426	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	I
P/H	0.6906	likely_pathogenic	0.6087	pathogenic	-0.856	Destabilizing	1.0	D	0.901	deleterious	N	0.470519411	None	None	I
P/I	0.6039	likely_pathogenic	0.5304	ambiguous	-0.487	Destabilizing	0.996	D	0.863	deleterious	None	None	None	None	I
P/K	0.8799	likely_pathogenic	0.8286	pathogenic	-0.975	Destabilizing	0.996	D	0.795	deleterious	None	None	None	None	I
P/L	0.3373	likely_benign	0.2702	benign	-0.487	Destabilizing	0.995	D	0.78	deleterious	N	0.50370135	None	None	I
P/M	0.6586	likely_pathogenic	0.5992	pathogenic	-0.421	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	I
P/N	0.7948	likely_pathogenic	0.7362	pathogenic	-0.789	Destabilizing	0.998	D	0.832	deleterious	None	None	None	None	I
P/Q	0.6266	likely_pathogenic	0.5514	ambiguous	-0.945	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	I
P/R	0.7708	likely_pathogenic	0.6943	pathogenic	-0.449	Destabilizing	0.998	D	0.873	deleterious	N	0.481115247	None	None	I
P/S	0.3903	ambiguous	0.3289	benign	-1.295	Destabilizing	0.99	D	0.817	deleterious	N	0.489849406	None	None	I
P/T	0.321	likely_benign	0.2669	benign	-1.199	Destabilizing	0.635	D	0.391	neutral	N	0.456910268	None	None	I
P/V	0.4217	ambiguous	0.3707	ambiguous	-0.669	Destabilizing	0.996	D	0.754	deleterious	None	None	None	None	I
P/W	0.9469	likely_pathogenic	0.9246	pathogenic	-1.019	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	I
P/Y	0.8734	likely_pathogenic	0.8298	pathogenic	-0.724	Destabilizing	1.0	D	0.902	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.