TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2142	6649;6650;6651	chr2:178775440;178775439;178775438	chr2:179640167;179640166;179640165
N2AB	2142	6649;6650;6651	chr2:178775440;178775439;178775438	chr2:179640167;179640166;179640165
N2A	2142	6649;6650;6651	chr2:178775440;178775439;178775438	chr2:179640167;179640166;179640165
N2B	2096	6511;6512;6513	chr2:178775440;178775439;178775438	chr2:179640167;179640166;179640165
Novex-1	2096	6511;6512;6513	chr2:178775440;178775439;178775438	chr2:179640167;179640166;179640165
Novex-2	2096	6511;6512;6513	chr2:178775440;178775439;178775438	chr2:179640167;179640166;179640165
Novex-3	2142	6649;6650;6651	chr2:178775440;178775439;178775438	chr2:179640167;179640166;179640165

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-10
• Domain position: 65
• Structural Position: 145
• Q(SASA): 0.3314
• 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
T/S	None	None	0.946	N	0.418	0.14	0.288727942641	gnomAD-4.0.0	6.84114E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99306E-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
T/A	0.0913	likely_benign	0.1	benign	-0.66	Destabilizing	0.64	D	0.44	neutral	N	0.510680428	None	None	N
T/C	0.3682	ambiguous	0.4223	ambiguous	-0.449	Destabilizing	0.999	D	0.547	neutral	None	None	None	None	N
T/D	0.3176	likely_benign	0.3689	ambiguous	-0.877	Destabilizing	0.996	D	0.54	neutral	None	None	None	None	N
T/E	0.2901	likely_benign	0.3102	benign	-0.902	Destabilizing	0.988	D	0.499	neutral	None	None	None	None	N
T/F	0.2448	likely_benign	0.3053	benign	-0.98	Destabilizing	0.976	D	0.655	neutral	None	None	None	None	N
T/G	0.1771	likely_benign	0.195	benign	-0.873	Destabilizing	0.988	D	0.559	neutral	None	None	None	None	N
T/H	0.2388	likely_benign	0.2731	benign	-1.271	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
T/I	0.2338	likely_benign	0.2817	benign	-0.191	Destabilizing	0.103	N	0.239	neutral	N	0.514136682	None	None	N
T/K	0.1867	likely_benign	0.1906	benign	-0.687	Destabilizing	0.988	D	0.497	neutral	None	None	None	None	N
T/L	0.0957	likely_benign	0.1094	benign	-0.191	Destabilizing	0.034	N	0.198	neutral	None	None	None	None	N
T/M	0.0941	likely_benign	0.1011	benign	0.309	Stabilizing	0.976	D	0.554	neutral	None	None	None	None	N
T/N	0.1098	likely_benign	0.1257	benign	-0.705	Destabilizing	0.995	D	0.507	neutral	N	0.501546609	None	None	N
T/P	0.5415	ambiguous	0.5995	pathogenic	-0.317	Destabilizing	0.995	D	0.547	neutral	D	0.650498563	None	None	N
T/Q	0.1943	likely_benign	0.2021	benign	-1.015	Destabilizing	0.996	D	0.55	neutral	None	None	None	None	N
T/R	0.1852	likely_benign	0.1935	benign	-0.339	Destabilizing	0.996	D	0.549	neutral	None	None	None	None	N
T/S	0.0836	likely_benign	0.0919	benign	-0.859	Destabilizing	0.946	D	0.418	neutral	N	0.503463507	None	None	N
T/V	0.161	likely_benign	0.1891	benign	-0.317	Destabilizing	0.034	N	0.168	neutral	None	None	None	None	N
T/W	0.6316	likely_pathogenic	0.7053	pathogenic	-0.947	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
T/Y	0.3229	likely_benign	0.3953	ambiguous	-0.664	Destabilizing	0.996	D	0.648	neutral	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.