TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14911	44956;44957;44958	chr2:178624549;178624548;178624547	chr2:179489276;179489275;179489274
N2AB	13270	40033;40034;40035	chr2:178624549;178624548;178624547	chr2:179489276;179489275;179489274
N2A	12343	37252;37253;37254	chr2:178624549;178624548;178624547	chr2:179489276;179489275;179489274
N2B	5846	17761;17762;17763	chr2:178624549;178624548;178624547	chr2:179489276;179489275;179489274
Novex-1	5971	18136;18137;18138	chr2:178624549;178624548;178624547	chr2:179489276;179489275;179489274
Novex-2	6038	18337;18338;18339	chr2:178624549;178624548;178624547	chr2:179489276;179489275;179489274
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-100
• Domain position: 59
• Structural Position: 140
• Q(SASA): 0.0876
• 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/K	rs754905274	-2.611	0.999	D	0.821	0.837	0.939999114054	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/K	rs754905274	-2.611	0.999	D	0.821	0.837	0.939999114054	gnomAD-4.0.0	1.59342E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4332E-05	0
I/M	rs751425454	-1.48	0.998	D	0.665	0.612	0.73347288092	gnomAD-2.1.1	3.23E-05	None	None	None	None	N	None	0	0	None	0	0	None	2.61489E-04	None	0	0	0
I/M	rs751425454	-1.48	0.998	D	0.665	0.612	0.73347288092	gnomAD-4.0.0	1.43767E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.43523E-04	0
I/T	rs754905274	-3.419	0.989	D	0.724	0.722	0.876608931427	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
I/T	rs754905274	-3.419	0.989	D	0.724	0.722	0.876608931427	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/T	rs754905274	-3.419	0.989	D	0.724	0.722	0.876608931427	gnomAD-4.0.0	6.57921E-06	None	None	None	None	N	None	2.41348E-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	0.9748	likely_pathogenic	0.9818	pathogenic	-2.966	Highly Destabilizing	0.992	D	0.671	neutral	None	None	None	None	N
I/C	0.97	likely_pathogenic	0.9798	pathogenic	-2.3	Highly Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
I/D	0.9984	likely_pathogenic	0.9988	pathogenic	-3.688	Highly Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
I/E	0.9951	likely_pathogenic	0.9964	pathogenic	-3.39	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
I/F	0.5984	likely_pathogenic	0.6614	pathogenic	-1.701	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
I/G	0.9952	likely_pathogenic	0.9964	pathogenic	-3.531	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
I/H	0.9892	likely_pathogenic	0.9916	pathogenic	-3.164	Highly Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
I/K	0.9847	likely_pathogenic	0.9886	pathogenic	-2.332	Highly Destabilizing	0.999	D	0.821	deleterious	D	0.813863115	None	None	N
I/L	0.3252	likely_benign	0.4111	ambiguous	-1.255	Destabilizing	0.889	D	0.415	neutral	D	0.622503119	None	None	N
I/M	0.4391	ambiguous	0.5289	ambiguous	-1.467	Destabilizing	0.998	D	0.665	neutral	D	0.72452887	None	None	N
I/N	0.9771	likely_pathogenic	0.9797	pathogenic	-2.993	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
I/P	0.9964	likely_pathogenic	0.9972	pathogenic	-1.819	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
I/Q	0.9886	likely_pathogenic	0.9917	pathogenic	-2.678	Highly Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
I/R	0.9766	likely_pathogenic	0.9812	pathogenic	-2.261	Highly Destabilizing	0.999	D	0.84	deleterious	D	0.813863114	None	None	N
I/S	0.974	likely_pathogenic	0.9777	pathogenic	-3.522	Highly Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
I/T	0.9686	likely_pathogenic	0.9786	pathogenic	-3.081	Highly Destabilizing	0.989	D	0.724	prob.delet.	D	0.722410158	None	None	N
I/V	0.2371	likely_benign	0.2554	benign	-1.819	Destabilizing	0.333	N	0.269	neutral	D	0.541592401	None	None	N
I/W	0.9874	likely_pathogenic	0.9924	pathogenic	-2.165	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
I/Y	0.9527	likely_pathogenic	0.9617	pathogenic	-2.025	Highly Destabilizing	1.0	D	0.737	prob.delet.	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.