TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24266	73021;73022;73023	chr2:178573336;178573335;178573334	chr2:179438063;179438062;179438061
N2AB	22625	68098;68099;68100	chr2:178573336;178573335;178573334	chr2:179438063;179438062;179438061
N2A	21698	65317;65318;65319	chr2:178573336;178573335;178573334	chr2:179438063;179438062;179438061
N2B	15201	45826;45827;45828	chr2:178573336;178573335;178573334	chr2:179438063;179438062;179438061
Novex-1	15326	46201;46202;46203	chr2:178573336;178573335;178573334	chr2:179438063;179438062;179438061
Novex-2	15393	46402;46403;46404	chr2:178573336;178573335;178573334	chr2:179438063;179438062;179438061
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-64
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.3757
• 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
G/D	None	None	1.0	N	0.586	0.442	0.38342384377	gnomAD-4.0.0	3.54643E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.93097E-05	0	0	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
G/A	0.2045	likely_benign	0.1545	benign	-0.311	Destabilizing	1.0	D	0.513	neutral	N	0.495524584	None	None	N
G/C	0.3516	ambiguous	0.244	benign	-0.882	Destabilizing	1.0	D	0.729	prob.delet.	N	0.507448709	None	None	N
G/D	0.7975	likely_pathogenic	0.63	pathogenic	-0.735	Destabilizing	1.0	D	0.586	neutral	N	0.510683251	None	None	N
G/E	0.77	likely_pathogenic	0.5989	pathogenic	-0.907	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
G/F	0.8173	likely_pathogenic	0.6796	pathogenic	-1.075	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
G/H	0.7487	likely_pathogenic	0.6192	pathogenic	-0.536	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
G/I	0.5923	likely_pathogenic	0.4033	ambiguous	-0.5	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
G/K	0.888	likely_pathogenic	0.7929	pathogenic	-0.876	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
G/L	0.6255	likely_pathogenic	0.4693	ambiguous	-0.5	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
G/M	0.7044	likely_pathogenic	0.5643	pathogenic	-0.526	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
G/N	0.5244	ambiguous	0.4015	ambiguous	-0.491	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
G/P	0.9796	likely_pathogenic	0.9484	pathogenic	-0.406	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
G/Q	0.7145	likely_pathogenic	0.5797	pathogenic	-0.806	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
G/R	0.7747	likely_pathogenic	0.6242	pathogenic	-0.39	Destabilizing	1.0	D	0.681	prob.neutral	N	0.507645733	None	None	N
G/S	0.1047	likely_benign	0.0872	benign	-0.599	Destabilizing	1.0	D	0.641	neutral	N	0.410249685	None	None	N
G/T	0.2717	likely_benign	0.1985	benign	-0.71	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
G/V	0.4265	ambiguous	0.2725	benign	-0.406	Destabilizing	1.0	D	0.707	prob.neutral	N	0.477734659	None	None	N
G/W	0.7673	likely_pathogenic	0.5995	pathogenic	-1.208	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
G/Y	0.7734	likely_pathogenic	0.6147	pathogenic	-0.878	Destabilizing	1.0	D	0.705	prob.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.