TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2630	8113;8114;8115	chr2:178771439;178771438;178771437	chr2:179636166;179636165;179636164
N2AB	2630	8113;8114;8115	chr2:178771439;178771438;178771437	chr2:179636166;179636165;179636164
N2A	2630	8113;8114;8115	chr2:178771439;178771438;178771437	chr2:179636166;179636165;179636164
N2B	2584	7975;7976;7977	chr2:178771439;178771438;178771437	chr2:179636166;179636165;179636164
Novex-1	2584	7975;7976;7977	chr2:178771439;178771438;178771437	chr2:179636166;179636165;179636164
Novex-2	2584	7975;7976;7977	chr2:178771439;178771438;178771437	chr2:179636166;179636165;179636164
Novex-3	2630	8113;8114;8115	chr2:178771439;178771438;178771437	chr2:179636166;179636165;179636164

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-16
• Domain position: 10
• Structural Position: 14
• Q(SASA): 0.6293
• 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	rs2091468969	None	0.374	N	0.319	0.211	0.251116650651	gnomAD-4.0.0	1.59105E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41429E-04	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
T/A	0.1309	likely_benign	0.1363	benign	-0.466	Destabilizing	0.76	D	0.411	neutral	D	0.547333665	None	None	N
T/C	0.6498	likely_pathogenic	0.6527	pathogenic	-0.395	Destabilizing	0.999	D	0.536	neutral	None	None	None	None	N
T/D	0.4638	ambiguous	0.4673	ambiguous	0.03	Stabilizing	0.986	D	0.491	neutral	None	None	None	None	N
T/E	0.3367	likely_benign	0.3358	benign	-0.011	Destabilizing	0.986	D	0.482	neutral	None	None	None	None	N
T/F	0.3128	likely_benign	0.3346	benign	-0.706	Destabilizing	0.986	D	0.617	neutral	None	None	None	None	N
T/G	0.5153	ambiguous	0.5383	ambiguous	-0.665	Destabilizing	0.953	D	0.467	neutral	None	None	None	None	N
T/H	0.3278	likely_benign	0.3268	benign	-0.923	Destabilizing	0.999	D	0.6	neutral	None	None	None	None	N
T/I	0.1313	likely_benign	0.1407	benign	-0.049	Destabilizing	0.1	N	0.26	neutral	N	0.507601806	None	None	N
T/K	0.2497	likely_benign	0.235	benign	-0.605	Destabilizing	0.986	D	0.489	neutral	None	None	None	None	N
T/L	0.127	likely_benign	0.1346	benign	-0.049	Destabilizing	0.91	D	0.404	neutral	None	None	None	None	N
T/M	0.0913	likely_benign	0.0973	benign	0.041	Stabilizing	0.996	D	0.531	neutral	None	None	None	None	N
T/N	0.1614	likely_benign	0.1689	benign	-0.442	Destabilizing	0.982	D	0.447	neutral	D	0.531735319	None	None	N
T/P	0.4046	ambiguous	0.3799	ambiguous	-0.156	Destabilizing	0.991	D	0.545	neutral	D	0.652907407	None	None	N
T/Q	0.2928	likely_benign	0.2925	benign	-0.619	Destabilizing	0.993	D	0.535	neutral	None	None	None	None	N
T/R	0.2273	likely_benign	0.2114	benign	-0.332	Destabilizing	0.993	D	0.541	neutral	None	None	None	None	N
T/S	0.1828	likely_benign	0.196	benign	-0.667	Destabilizing	0.374	N	0.319	neutral	N	0.50917363	None	None	N
T/V	0.1151	likely_benign	0.1233	benign	-0.156	Destabilizing	0.91	D	0.386	neutral	None	None	None	None	N
T/W	0.6758	likely_pathogenic	0.6793	pathogenic	-0.694	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
T/Y	0.388	ambiguous	0.3898	ambiguous	-0.441	Destabilizing	0.998	D	0.627	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.