TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19589	58990;58991;58992	chr2:178593443;178593442;178593441	chr2:179458170;179458169;179458168
N2AB	17948	54067;54068;54069	chr2:178593443;178593442;178593441	chr2:179458170;179458169;179458168
N2A	17021	51286;51287;51288	chr2:178593443;178593442;178593441	chr2:179458170;179458169;179458168
N2B	10524	31795;31796;31797	chr2:178593443;178593442;178593441	chr2:179458170;179458169;179458168
Novex-1	10649	32170;32171;32172	chr2:178593443;178593442;178593441	chr2:179458170;179458169;179458168
Novex-2	10716	32371;32372;32373	chr2:178593443;178593442;178593441	chr2:179458170;179458169;179458168
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-30
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.5011
• 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/K	None	None	0.001	N	0.149	0.192	0.273938319068	gnomAD-4.0.0	1.36923E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79928E-05	0	0
T/R	None	None	0.473	N	0.353	0.234	0.344483371355	gnomAD-4.0.0	6.84614E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.1632E-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
T/A	0.0998	likely_benign	0.0982	benign	-0.515	Destabilizing	0.425	N	0.257	neutral	N	0.51234505	None	None	N
T/C	0.4151	ambiguous	0.4371	ambiguous	-0.363	Destabilizing	0.995	D	0.391	neutral	None	None	None	None	N
T/D	0.3892	ambiguous	0.4092	ambiguous	0.291	Stabilizing	0.704	D	0.341	neutral	None	None	None	None	N
T/E	0.2644	likely_benign	0.2819	benign	0.262	Stabilizing	0.329	N	0.341	neutral	None	None	None	None	N
T/F	0.2792	likely_benign	0.2825	benign	-0.698	Destabilizing	0.893	D	0.457	neutral	None	None	None	None	N
T/G	0.239	likely_benign	0.2424	benign	-0.729	Destabilizing	0.704	D	0.373	neutral	None	None	None	None	N
T/H	0.2496	likely_benign	0.2634	benign	-0.963	Destabilizing	0.981	D	0.417	neutral	None	None	None	None	N
T/I	0.1956	likely_benign	0.1955	benign	-0.054	Destabilizing	0.473	N	0.345	neutral	N	0.510112822	None	None	N
T/K	0.1779	likely_benign	0.1876	benign	-0.479	Destabilizing	0.001	N	0.149	neutral	N	0.460934795	None	None	N
T/L	0.1083	likely_benign	0.1089	benign	-0.054	Destabilizing	0.003	N	0.141	neutral	None	None	None	None	N
T/M	0.0925	likely_benign	0.0898	benign	0.054	Stabilizing	0.893	D	0.423	neutral	None	None	None	None	N
T/N	0.1408	likely_benign	0.1438	benign	-0.338	Destabilizing	0.704	D	0.28	neutral	None	None	None	None	N
T/P	0.5368	ambiguous	0.5173	ambiguous	-0.176	Destabilizing	0.784	D	0.421	neutral	N	0.483071166	None	None	N
T/Q	0.1918	likely_benign	0.2093	benign	-0.501	Destabilizing	0.704	D	0.423	neutral	None	None	None	None	N
T/R	0.1778	likely_benign	0.1807	benign	-0.253	Destabilizing	0.473	N	0.353	neutral	N	0.51523064	None	None	N
T/S	0.1098	likely_benign	0.1159	benign	-0.632	Destabilizing	0.425	N	0.347	neutral	N	0.425280639	None	None	N
T/V	0.1448	likely_benign	0.1466	benign	-0.176	Destabilizing	0.329	N	0.325	neutral	None	None	None	None	N
T/W	0.5835	likely_pathogenic	0.5911	pathogenic	-0.657	Destabilizing	0.995	D	0.434	neutral	None	None	None	None	N
T/Y	0.3069	likely_benign	0.3241	benign	-0.405	Destabilizing	0.981	D	0.449	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.