TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33250	99973;99974;99975	chr2:178537459;178537458;178537457	chr2:179402186;179402185;179402184
N2AB	31609	95050;95051;95052	chr2:178537459;178537458;178537457	chr2:179402186;179402185;179402184
N2A	30682	92269;92270;92271	chr2:178537459;178537458;178537457	chr2:179402186;179402185;179402184
N2B	24185	72778;72779;72780	chr2:178537459;178537458;178537457	chr2:179402186;179402185;179402184
Novex-1	24310	73153;73154;73155	chr2:178537459;178537458;178537457	chr2:179402186;179402185;179402184
Novex-2	24377	73354;73355;73356	chr2:178537459;178537458;178537457	chr2:179402186;179402185;179402184
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-157
• Domain position: 48
• Structural Position: 134
• Q(SASA): 0.259
• 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
H/R	rs1395830573	-1.039	0.465	N	0.319	0.178	0.225215365344	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.6E-05	None	0	None	0	0	0
H/R	rs1395830573	-1.039	0.465	N	0.319	0.178	0.225215365344	gnomAD-4.0.0	3.18457E-06	None	None	None	None	N	None	0	0	None	0	2.77701E-05	None	0	0	0	1.4339E-05	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
H/A	0.4684	ambiguous	0.5322	ambiguous	-0.484	Destabilizing	0.343	N	0.493	neutral	None	None	None	None	N
H/C	0.3653	ambiguous	0.3998	ambiguous	0.297	Stabilizing	0.993	D	0.518	neutral	None	None	None	None	N
H/D	0.3383	likely_benign	0.384	ambiguous	-0.668	Destabilizing	0.351	N	0.423	neutral	N	0.436124856	None	None	N
H/E	0.5214	ambiguous	0.5477	ambiguous	-0.57	Destabilizing	0.331	N	0.351	neutral	None	None	None	None	N
H/F	0.4072	ambiguous	0.4535	ambiguous	0.826	Stabilizing	0.986	D	0.453	neutral	None	None	None	None	N
H/G	0.4745	ambiguous	0.5386	ambiguous	-0.837	Destabilizing	0.705	D	0.521	neutral	None	None	None	None	N
H/I	0.5684	likely_pathogenic	0.6232	pathogenic	0.488	Stabilizing	0.942	D	0.519	neutral	None	None	None	None	N
H/K	0.4504	ambiguous	0.4488	ambiguous	-0.215	Destabilizing	0.322	N	0.433	neutral	None	None	None	None	N
H/L	0.248	likely_benign	0.2651	benign	0.488	Stabilizing	0.634	D	0.514	neutral	N	0.486343033	None	None	N
H/M	0.6237	likely_pathogenic	0.6481	pathogenic	0.248	Stabilizing	0.942	D	0.517	neutral	None	None	None	None	N
H/N	0.0758	likely_benign	0.1132	benign	-0.524	Destabilizing	0.351	N	0.333	neutral	N	0.415384224	None	None	N
H/P	0.7028	likely_pathogenic	0.6996	pathogenic	0.184	Stabilizing	0.726	D	0.513	neutral	N	0.456886917	None	None	N
H/Q	0.2917	likely_benign	0.3458	ambiguous	-0.317	Destabilizing	0.024	N	0.242	neutral	N	0.447862002	None	None	N
H/R	0.2281	likely_benign	0.248	benign	-0.722	Destabilizing	0.465	N	0.319	neutral	N	0.456020126	None	None	N
H/S	0.2947	likely_benign	0.3751	ambiguous	-0.424	Destabilizing	0.031	N	0.255	neutral	None	None	None	None	N
H/T	0.3557	ambiguous	0.4372	ambiguous	-0.217	Destabilizing	0.264	N	0.503	neutral	None	None	None	None	N
H/V	0.5065	ambiguous	0.5489	ambiguous	0.184	Stabilizing	0.706	D	0.529	neutral	None	None	None	None	N
H/W	0.6205	likely_pathogenic	0.6064	pathogenic	1.116	Stabilizing	0.999	D	0.531	neutral	None	None	None	None	N
H/Y	0.1174	likely_benign	0.1378	benign	1.129	Stabilizing	0.831	D	0.388	neutral	N	0.408498325	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.