TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35346	106261;106262;106263	chr2:178530579;178530578;178530577	chr2:179395306;179395305;179395304
N2AB	33705	101338;101339;101340	chr2:178530579;178530578;178530577	chr2:179395306;179395305;179395304
N2A	32778	98557;98558;98559	chr2:178530579;178530578;178530577	chr2:179395306;179395305;179395304
N2B	26281	79066;79067;79068	chr2:178530579;178530578;178530577	chr2:179395306;179395305;179395304
Novex-1	26406	79441;79442;79443	chr2:178530579;178530578;178530577	chr2:179395306;179395305;179395304
Novex-2	26473	79642;79643;79644	chr2:178530579;178530578;178530577	chr2:179395306;179395305;179395304
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-165
• Domain position: 61
• Structural Position: 140
• Q(SASA): 0.0521
• 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
I/M	rs1688672739	None	0.999	D	0.678	0.563	0.713815690768	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/M	rs1688672739	None	0.999	D	0.678	0.563	0.713815690768	gnomAD-4.0.0	6.5703E-06	None	None	None	None	N	None	2.41266E-05	0	None	0	0	None	0	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
I/A	0.9608	likely_pathogenic	0.954	pathogenic	-3.188	Highly Destabilizing	0.964	D	0.69	prob.neutral	None	None	None	None	N
I/C	0.9708	likely_pathogenic	0.9683	pathogenic	-2.449	Highly Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
I/D	0.995	likely_pathogenic	0.9929	pathogenic	-3.911	Highly Destabilizing	0.998	D	0.883	deleterious	None	None	None	None	N
I/E	0.9853	likely_pathogenic	0.9801	pathogenic	-3.612	Highly Destabilizing	0.999	D	0.895	deleterious	None	None	None	None	N
I/F	0.5368	ambiguous	0.5128	ambiguous	-1.889	Destabilizing	0.999	D	0.705	prob.neutral	D	0.550201207	None	None	N
I/G	0.9892	likely_pathogenic	0.9866	pathogenic	-3.767	Highly Destabilizing	0.171	N	0.637	neutral	None	None	None	None	N
I/H	0.9812	likely_pathogenic	0.9753	pathogenic	-3.321	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
I/K	0.9637	likely_pathogenic	0.9494	pathogenic	-2.611	Highly Destabilizing	0.998	D	0.893	deleterious	None	None	None	None	N
I/L	0.3177	likely_benign	0.3028	benign	-1.437	Destabilizing	0.992	D	0.458	neutral	D	0.539744874	None	None	N
I/M	0.2274	likely_benign	0.2192	benign	-1.545	Destabilizing	0.999	D	0.678	prob.neutral	D	0.606910103	None	None	N
I/N	0.9427	likely_pathogenic	0.9216	pathogenic	-3.242	Highly Destabilizing	0.997	D	0.893	deleterious	D	0.633860844	None	None	N
I/P	0.9956	likely_pathogenic	0.9941	pathogenic	-2.013	Highly Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
I/Q	0.9728	likely_pathogenic	0.9643	pathogenic	-2.953	Highly Destabilizing	0.999	D	0.906	deleterious	None	None	None	None	N
I/R	0.9519	likely_pathogenic	0.9367	pathogenic	-2.432	Highly Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
I/S	0.9646	likely_pathogenic	0.9564	pathogenic	-3.816	Highly Destabilizing	0.98	D	0.824	deleterious	D	0.617609319	None	None	N
I/T	0.9679	likely_pathogenic	0.9614	pathogenic	-3.372	Highly Destabilizing	0.997	D	0.757	deleterious	D	0.61720571	None	None	N
I/V	0.2638	likely_benign	0.2632	benign	-2.013	Highly Destabilizing	0.992	D	0.404	neutral	D	0.548274245	None	None	N
I/W	0.9689	likely_pathogenic	0.9626	pathogenic	-2.359	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
I/Y	0.9074	likely_pathogenic	0.8889	pathogenic	-2.199	Highly Destabilizing	0.999	D	0.764	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.