TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22618	68077;68078;68079	chr2:178579178;178579177;178579176	chr2:179443905;179443904;179443903
N2AB	20977	63154;63155;63156	chr2:178579178;178579177;178579176	chr2:179443905;179443904;179443903
N2A	20050	60373;60374;60375	chr2:178579178;178579177;178579176	chr2:179443905;179443904;179443903
N2B	13553	40882;40883;40884	chr2:178579178;178579177;178579176	chr2:179443905;179443904;179443903
Novex-1	13678	41257;41258;41259	chr2:178579178;178579177;178579176	chr2:179443905;179443904;179443903
Novex-2	13745	41458;41459;41460	chr2:178579178;178579177;178579176	chr2:179443905;179443904;179443903
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-127
• Domain position: 59
• Structural Position: 151
• Q(SASA): 0.2337
• 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
A/T	None	None	1.0	N	0.726	0.414	0.414798848334	gnomAD-4.0.0	1.59182E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85945E-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
A/C	0.555	ambiguous	0.5549	ambiguous	-0.88	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
A/D	0.5927	likely_pathogenic	0.589	pathogenic	-0.353	Destabilizing	1.0	D	0.801	deleterious	N	0.501470088	None	None	N
A/E	0.4646	ambiguous	0.4467	ambiguous	-0.445	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
A/F	0.5382	ambiguous	0.5431	ambiguous	-0.984	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
A/G	0.1386	likely_benign	0.142	benign	-0.824	Destabilizing	1.0	D	0.582	neutral	D	0.535291773	None	None	N
A/H	0.6639	likely_pathogenic	0.6713	pathogenic	-0.839	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
A/I	0.4919	ambiguous	0.4742	ambiguous	-0.398	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
A/K	0.6973	likely_pathogenic	0.677	pathogenic	-0.81	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
A/L	0.3909	ambiguous	0.3816	ambiguous	-0.398	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
A/M	0.3525	ambiguous	0.3474	ambiguous	-0.395	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
A/N	0.457	ambiguous	0.4664	ambiguous	-0.511	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
A/P	0.9326	likely_pathogenic	0.933	pathogenic	-0.446	Destabilizing	1.0	D	0.814	deleterious	D	0.532198096	None	None	N
A/Q	0.4955	ambiguous	0.4818	ambiguous	-0.718	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
A/R	0.5732	likely_pathogenic	0.5593	ambiguous	-0.437	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
A/S	0.0921	likely_benign	0.1013	benign	-0.884	Destabilizing	1.0	D	0.607	neutral	N	0.471912298	None	None	N
A/T	0.1178	likely_benign	0.118	benign	-0.877	Destabilizing	1.0	D	0.726	prob.delet.	N	0.500928483	None	None	N
A/V	0.2656	likely_benign	0.2566	benign	-0.446	Destabilizing	1.0	D	0.674	neutral	N	0.496950638	None	None	N
A/W	0.8957	likely_pathogenic	0.8966	pathogenic	-1.176	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
A/Y	0.6951	likely_pathogenic	0.6797	pathogenic	-0.802	Destabilizing	1.0	D	0.821	deleterious	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.