TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24218	72877;72878;72879	chr2:178573480;178573479;178573478	chr2:179438207;179438206;179438205
N2AB	22577	67954;67955;67956	chr2:178573480;178573479;178573478	chr2:179438207;179438206;179438205
N2A	21650	65173;65174;65175	chr2:178573480;178573479;178573478	chr2:179438207;179438206;179438205
N2B	15153	45682;45683;45684	chr2:178573480;178573479;178573478	chr2:179438207;179438206;179438205
Novex-1	15278	46057;46058;46059	chr2:178573480;178573479;178573478	chr2:179438207;179438206;179438205
Novex-2	15345	46258;46259;46260	chr2:178573480;178573479;178573478	chr2:179438207;179438206;179438205
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-63
• Domain position: 97
• Structural Position: 132
• Q(SASA): 1.4111
• 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
N/K	None	None	0.115	N	0.748	0.132	0.137902524267	gnomAD-4.0.0	1.47595E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.87968E-06	0	0
N/Y	None	None	0.186	N	0.622	0.17	0.225902525712	gnomAD-4.0.0	1.47592E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.87965E-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
N/A	0.5112	ambiguous	0.5003	ambiguous	-0.142	Destabilizing	0.147	N	0.604	neutral	None	None	None	None	I
N/C	0.5736	likely_pathogenic	0.5631	ambiguous	0.309	Stabilizing	0.934	D	0.761	deleterious	None	None	None	None	I
N/D	0.1042	likely_benign	0.1075	benign	0.172	Stabilizing	None	N	0.319	neutral	N	0.434801413	None	None	I
N/E	0.6382	likely_pathogenic	0.6399	pathogenic	0.111	Stabilizing	0.08	N	0.713	prob.delet.	None	None	None	None	I
N/F	0.7404	likely_pathogenic	0.7374	pathogenic	-0.705	Destabilizing	0.552	D	0.644	neutral	None	None	None	None	I
N/G	0.6738	likely_pathogenic	0.6593	pathogenic	-0.25	Destabilizing	0.147	N	0.715	prob.delet.	None	None	None	None	I
N/H	0.2082	likely_benign	0.2241	benign	-0.335	Destabilizing	0.001	N	0.462	neutral	N	0.511472685	None	None	I
N/I	0.4204	ambiguous	0.4126	ambiguous	0.044	Stabilizing	0.481	N	0.664	prob.neutral	N	0.467905156	None	None	I
N/K	0.7761	likely_pathogenic	0.7783	pathogenic	0.214	Stabilizing	0.115	N	0.748	deleterious	N	0.46265169	None	None	I
N/L	0.4039	ambiguous	0.4029	ambiguous	0.044	Stabilizing	0.378	N	0.657	prob.neutral	None	None	None	None	I
N/M	0.5292	ambiguous	0.5298	ambiguous	0.268	Stabilizing	0.934	D	0.639	neutral	None	None	None	None	I
N/P	0.7036	likely_pathogenic	0.6867	pathogenic	0.006	Stabilizing	0.552	D	0.649	prob.neutral	None	None	None	None	I
N/Q	0.6708	likely_pathogenic	0.6685	pathogenic	-0.2	Destabilizing	0.378	N	0.756	deleterious	None	None	None	None	I
N/R	0.8116	likely_pathogenic	0.8164	pathogenic	0.247	Stabilizing	0.378	N	0.758	deleterious	None	None	None	None	I
N/S	0.1259	likely_benign	0.1266	benign	0.042	Stabilizing	0.061	N	0.723	deleterious	N	0.511299326	None	None	I
N/T	0.294	likely_benign	0.2886	benign	0.104	Stabilizing	0.115	N	0.748	deleterious	N	0.460683213	None	None	I
N/V	0.4625	ambiguous	0.4434	ambiguous	0.006	Stabilizing	0.552	D	0.686	prob.delet.	None	None	None	None	I
N/W	0.9143	likely_pathogenic	0.9206	pathogenic	-0.794	Destabilizing	0.934	D	0.787	deleterious	None	None	None	None	I
N/Y	0.3368	likely_benign	0.3425	ambiguous	-0.477	Destabilizing	0.186	N	0.622	neutral	N	0.516590503	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.