TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13689	41290;41291;41292	chr2:178636662;178636661;178636660	chr2:179501389;179501388;179501387
N2AB	12048	36367;36368;36369	chr2:178636662;178636661;178636660	chr2:179501389;179501388;179501387
N2A	11121	33586;33587;33588	chr2:178636662;178636661;178636660	chr2:179501389;179501388;179501387
N2B	4624	14095;14096;14097	chr2:178636662;178636661;178636660	chr2:179501389;179501388;179501387
Novex-1	4749	14470;14471;14472	chr2:178636662;178636661;178636660	chr2:179501389;179501388;179501387
Novex-2	4816	14671;14672;14673	chr2:178636662;178636661;178636660	chr2:179501389;179501388;179501387
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-87
• Domain position: 6
• Structural Position: 8
• Q(SASA): 0.3504
• Predicted PPI site: I

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/F	rs1316196026	-0.961	0.934	D	0.473	0.272	0.530309751445	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
I/F	rs1316196026	-0.961	0.934	D	0.473	0.272	0.530309751445	gnomAD-4.0.0	1.16346E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.43942E-05	0	1.65728E-05

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	0.9626	likely_pathogenic	0.9658	pathogenic	-2.348	Highly Destabilizing	0.688	D	0.404	neutral	None	None	None	None	I
I/C	0.9882	likely_pathogenic	0.9889	pathogenic	-1.577	Destabilizing	0.998	D	0.569	neutral	None	None	None	None	I
I/D	0.9988	likely_pathogenic	0.9989	pathogenic	-2.497	Highly Destabilizing	0.991	D	0.646	neutral	None	None	None	None	I
I/E	0.9939	likely_pathogenic	0.995	pathogenic	-2.287	Highly Destabilizing	0.974	D	0.628	neutral	None	None	None	None	I
I/F	0.7766	likely_pathogenic	0.8163	pathogenic	-1.33	Destabilizing	0.934	D	0.473	neutral	D	0.562183336	None	None	I
I/G	0.9949	likely_pathogenic	0.9945	pathogenic	-2.874	Highly Destabilizing	0.974	D	0.627	neutral	None	None	None	None	I
I/H	0.9973	likely_pathogenic	0.9981	pathogenic	-2.324	Highly Destabilizing	0.998	D	0.638	neutral	None	None	None	None	I
I/K	0.9899	likely_pathogenic	0.9918	pathogenic	-1.583	Destabilizing	0.949	D	0.623	neutral	None	None	None	None	I
I/L	0.1942	likely_benign	0.1812	benign	-0.836	Destabilizing	0.002	N	0.15	neutral	N	0.391745066	None	None	I
I/M	0.1221	likely_benign	0.1541	benign	-0.843	Destabilizing	0.267	N	0.287	neutral	N	0.499196091	None	None	I
I/N	0.9779	likely_pathogenic	0.984	pathogenic	-1.857	Destabilizing	0.989	D	0.635	neutral	D	0.606077763	None	None	I
I/P	0.9885	likely_pathogenic	0.9756	pathogenic	-1.32	Destabilizing	0.991	D	0.644	neutral	None	None	None	None	I
I/Q	0.9854	likely_pathogenic	0.9903	pathogenic	-1.741	Destabilizing	0.974	D	0.634	neutral	None	None	None	None	I
I/R	0.9913	likely_pathogenic	0.9926	pathogenic	-1.344	Destabilizing	0.974	D	0.645	neutral	None	None	None	None	I
I/S	0.985	likely_pathogenic	0.9879	pathogenic	-2.563	Highly Destabilizing	0.891	D	0.559	neutral	D	0.540195118	None	None	I
I/T	0.9787	likely_pathogenic	0.9837	pathogenic	-2.213	Highly Destabilizing	0.801	D	0.456	neutral	D	0.562778757	None	None	I
I/V	0.4194	ambiguous	0.4158	ambiguous	-1.32	Destabilizing	0.022	N	0.192	neutral	N	0.5043865	None	None	I
I/W	0.9959	likely_pathogenic	0.9969	pathogenic	-1.705	Destabilizing	0.998	D	0.647	neutral	None	None	None	None	I
I/Y	0.9868	likely_pathogenic	0.991	pathogenic	-1.416	Destabilizing	0.974	D	0.586	neutral	None	None	None	None	I

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.