TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33244	99955;99956;99957	chr2:178537477;178537476;178537475	chr2:179402204;179402203;179402202
N2AB	31603	95032;95033;95034	chr2:178537477;178537476;178537475	chr2:179402204;179402203;179402202
N2A	30676	92251;92252;92253	chr2:178537477;178537476;178537475	chr2:179402204;179402203;179402202
N2B	24179	72760;72761;72762	chr2:178537477;178537476;178537475	chr2:179402204;179402203;179402202
Novex-1	24304	73135;73136;73137	chr2:178537477;178537476;178537475	chr2:179402204;179402203;179402202
Novex-2	24371	73336;73337;73338	chr2:178537477;178537476;178537475	chr2:179402204;179402203;179402202
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-157
• Domain position: 42
• Structural Position: 122
• Q(SASA): 0.3397
• 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/I	rs1282327572	-0.185	0.006	N	0.185	0.209	0.270447802918	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.65E-05	0	0
T/N	None	None	0.639	N	0.373	0.191	0.27855597813	gnomAD-4.0.0	1.59177E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85896E-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	0.0858	likely_benign	0.0873	benign	-0.998	Destabilizing	None	N	0.144	neutral	N	0.492095569	None	None	N
T/C	0.4163	ambiguous	0.4344	ambiguous	-0.771	Destabilizing	0.968	D	0.4	neutral	None	None	None	None	N
T/D	0.4319	ambiguous	0.4599	ambiguous	-0.672	Destabilizing	0.536	D	0.371	neutral	None	None	None	None	N
T/E	0.349	ambiguous	0.3558	ambiguous	-0.634	Destabilizing	0.523	D	0.351	neutral	None	None	None	None	N
T/F	0.2386	likely_benign	0.268	benign	-1.041	Destabilizing	0.967	D	0.434	neutral	None	None	None	None	N
T/G	0.338	likely_benign	0.3446	ambiguous	-1.281	Destabilizing	0.58	D	0.393	neutral	None	None	None	None	N
T/H	0.2558	likely_benign	0.2611	benign	-1.569	Destabilizing	0.992	D	0.461	neutral	None	None	None	None	N
T/I	0.1418	likely_benign	0.1443	benign	-0.32	Destabilizing	0.006	N	0.185	neutral	N	0.448691508	None	None	N
T/K	0.2663	likely_benign	0.2804	benign	-0.77	Destabilizing	0.605	D	0.351	neutral	None	None	None	None	N
T/L	0.1224	likely_benign	0.1267	benign	-0.32	Destabilizing	0.122	N	0.299	neutral	None	None	None	None	N
T/M	0.1069	likely_benign	0.1049	benign	-0.004	Destabilizing	0.916	D	0.407	neutral	None	None	None	None	N
T/N	0.1372	likely_benign	0.1439	benign	-0.876	Destabilizing	0.639	D	0.373	neutral	N	0.486380318	None	None	N
T/P	0.6256	likely_pathogenic	0.6385	pathogenic	-0.514	Destabilizing	0.466	N	0.381	neutral	N	0.483010211	None	None	N
T/Q	0.2444	likely_benign	0.2475	benign	-1.044	Destabilizing	0.836	D	0.409	neutral	None	None	None	None	N
T/R	0.2165	likely_benign	0.2268	benign	-0.587	Destabilizing	0.935	D	0.393	neutral	None	None	None	None	N
T/S	0.1149	likely_benign	0.1191	benign	-1.166	Destabilizing	0.016	N	0.337	neutral	N	0.454057256	None	None	N
T/V	0.1224	likely_benign	0.126	benign	-0.514	Destabilizing	0.006	N	0.148	neutral	None	None	None	None	N
T/W	0.6379	likely_pathogenic	0.6643	pathogenic	-0.965	Destabilizing	0.997	D	0.507	neutral	None	None	None	None	N
T/Y	0.2981	likely_benign	0.3204	benign	-0.704	Destabilizing	0.989	D	0.469	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.