TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14629	44110;44111;44112	chr2:178631163;178631162;178631161	chr2:179495890;179495889;179495888
N2AB	12988	39187;39188;39189	chr2:178631163;178631162;178631161	chr2:179495890;179495889;179495888
N2A	12061	36406;36407;36408	chr2:178631163;178631162;178631161	chr2:179495890;179495889;179495888
N2B	5564	16915;16916;16917	chr2:178631163;178631162;178631161	chr2:179495890;179495889;179495888
Novex-1	5689	17290;17291;17292	chr2:178631163;178631162;178631161	chr2:179495890;179495889;179495888
Novex-2	5756	17491;17492;17493	chr2:178631163;178631162;178631161	chr2:179495890;179495889;179495888
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-97
• Domain position: 44
• Structural Position: 111
• Q(SASA): 0.8379
• 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	0.904	N	0.408	0.146	0.26547132957	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

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	0.3227	likely_benign	0.3126	benign	-0.1	Destabilizing	0.754	D	0.446	neutral	None	None	None	None	I
K/C	0.8902	likely_pathogenic	0.8522	pathogenic	-0.561	Destabilizing	0.998	D	0.6	neutral	None	None	None	None	I
K/D	0.4594	ambiguous	0.4768	ambiguous	-0.354	Destabilizing	0.978	D	0.406	neutral	None	None	None	None	I
K/E	0.1408	likely_benign	0.1557	benign	-0.381	Destabilizing	0.822	D	0.426	neutral	N	0.443530257	None	None	I
K/F	0.8679	likely_pathogenic	0.8449	pathogenic	-0.511	Destabilizing	0.993	D	0.568	neutral	None	None	None	None	I
K/G	0.3865	ambiguous	0.3709	ambiguous	-0.183	Destabilizing	0.86	D	0.41	neutral	None	None	None	None	I
K/H	0.5069	ambiguous	0.4629	ambiguous	-0.276	Destabilizing	0.998	D	0.46	neutral	None	None	None	None	I
K/I	0.4505	ambiguous	0.4289	ambiguous	0.037	Stabilizing	0.942	D	0.569	neutral	D	0.592331885	None	None	I
K/L	0.4873	ambiguous	0.4709	ambiguous	0.037	Stabilizing	0.86	D	0.415	neutral	None	None	None	None	I
K/M	0.3682	ambiguous	0.3615	ambiguous	-0.213	Destabilizing	0.998	D	0.451	neutral	None	None	None	None	I
K/N	0.3992	ambiguous	0.3916	ambiguous	-0.127	Destabilizing	0.942	D	0.434	neutral	N	0.430207201	None	None	I
K/P	0.4731	ambiguous	0.4658	ambiguous	0.011	Stabilizing	0.019	N	0.343	neutral	None	None	None	None	I
K/Q	0.1798	likely_benign	0.17	benign	-0.261	Destabilizing	0.97	D	0.459	neutral	N	0.437401208	None	None	I
K/R	0.0971	likely_benign	0.087	benign	-0.243	Destabilizing	0.904	D	0.408	neutral	N	0.441027185	None	None	I
K/S	0.3969	ambiguous	0.3713	ambiguous	-0.474	Destabilizing	0.754	D	0.407	neutral	None	None	None	None	I
K/T	0.2414	likely_benign	0.2367	benign	-0.403	Destabilizing	0.058	N	0.337	neutral	N	0.46853619	None	None	I
K/V	0.4129	ambiguous	0.3897	ambiguous	0.011	Stabilizing	0.754	D	0.43	neutral	None	None	None	None	I
K/W	0.8615	likely_pathogenic	0.829	pathogenic	-0.625	Destabilizing	0.998	D	0.635	neutral	None	None	None	None	I
K/Y	0.7768	likely_pathogenic	0.7446	pathogenic	-0.287	Destabilizing	0.993	D	0.525	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.