TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15541	46846;46847;46848	chr2:178619696;178619695;178619694	chr2:179484423;179484422;179484421
N2AB	13900	41923;41924;41925	chr2:178619696;178619695;178619694	chr2:179484423;179484422;179484421
N2A	12973	39142;39143;39144	chr2:178619696;178619695;178619694	chr2:179484423;179484422;179484421
N2B	6476	19651;19652;19653	chr2:178619696;178619695;178619694	chr2:179484423;179484422;179484421
Novex-1	6601	20026;20027;20028	chr2:178619696;178619695;178619694	chr2:179484423;179484422;179484421
Novex-2	6668	20227;20228;20229	chr2:178619696;178619695;178619694	chr2:179484423;179484422;179484421
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-107
• Domain position: 62
• Structural Position: 144
• Q(SASA): 0.0658
• 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	rs2057981019	None	0.998	N	0.676	0.38	0.501559347837	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	0	6.58E-05	0	0	0	None	0	0	0	0	0
I/M	rs2057981019	None	0.998	N	0.676	0.38	0.501559347837	gnomAD-4.0.0	6.58536E-06	None	None	None	None	N	None	0	6.57549E-05	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	0.8092	likely_pathogenic	0.7322	pathogenic	-2.814	Highly Destabilizing	0.992	D	0.592	neutral	None	None	None	None	N
I/C	0.8774	likely_pathogenic	0.8479	pathogenic	-2.457	Highly Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
I/D	0.9944	likely_pathogenic	0.9922	pathogenic	-3.625	Highly Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
I/E	0.9859	likely_pathogenic	0.9804	pathogenic	-3.432	Highly Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
I/F	0.7379	likely_pathogenic	0.7295	pathogenic	-1.638	Destabilizing	0.998	D	0.701	prob.neutral	N	0.51718186	None	None	N
I/G	0.9708	likely_pathogenic	0.9557	pathogenic	-3.315	Highly Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
I/H	0.9814	likely_pathogenic	0.9792	pathogenic	-2.692	Highly Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
I/K	0.9588	likely_pathogenic	0.9548	pathogenic	-2.293	Highly Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
I/L	0.2838	likely_benign	0.2843	benign	-1.36	Destabilizing	0.889	D	0.393	neutral	N	0.492364449	None	None	N
I/M	0.291	likely_benign	0.2757	benign	-1.485	Destabilizing	0.998	D	0.676	prob.neutral	N	0.520162475	None	None	N
I/N	0.8996	likely_pathogenic	0.8789	pathogenic	-2.673	Highly Destabilizing	0.999	D	0.791	deleterious	N	0.518135557	None	None	N
I/P	0.955	likely_pathogenic	0.9487	pathogenic	-1.828	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
I/Q	0.9695	likely_pathogenic	0.9616	pathogenic	-2.581	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
I/R	0.9405	likely_pathogenic	0.9329	pathogenic	-1.886	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
I/S	0.8613	likely_pathogenic	0.8128	pathogenic	-3.276	Highly Destabilizing	0.998	D	0.744	deleterious	N	0.509496402	None	None	N
I/T	0.6528	likely_pathogenic	0.6073	pathogenic	-2.952	Highly Destabilizing	0.989	D	0.707	prob.neutral	N	0.505917299	None	None	N
I/V	0.1233	likely_benign	0.1293	benign	-1.828	Destabilizing	0.333	N	0.265	neutral	N	0.414587069	None	None	N
I/W	0.9883	likely_pathogenic	0.9871	pathogenic	-2.058	Highly Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
I/Y	0.9641	likely_pathogenic	0.9608	pathogenic	-1.867	Destabilizing	1.0	D	0.741	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.