TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35327	106204;106205;106206	chr2:178530636;178530635;178530634	chr2:179395363;179395362;179395361
N2AB	33686	101281;101282;101283	chr2:178530636;178530635;178530634	chr2:179395363;179395362;179395361
N2A	32759	98500;98501;98502	chr2:178530636;178530635;178530634	chr2:179395363;179395362;179395361
N2B	26262	79009;79010;79011	chr2:178530636;178530635;178530634	chr2:179395363;179395362;179395361
Novex-1	26387	79384;79385;79386	chr2:178530636;178530635;178530634	chr2:179395363;179395362;179395361
Novex-2	26454	79585;79586;79587	chr2:178530636;178530635;178530634	chr2:179395363;179395362;179395361
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-165
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.6946
• 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
K/M	rs1164792965	-0.29	1.0	N	0.5	0.556	0.407901774203	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/M	rs1164792965	-0.29	1.0	N	0.5	0.556	0.407901774203	gnomAD-4.0.0	1.59088E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-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
K/A	0.3792	ambiguous	0.3534	ambiguous	0.001	Stabilizing	0.871	D	0.487	neutral	None	None	None	None	N
K/C	0.8243	likely_pathogenic	0.7833	pathogenic	-0.448	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	N
K/D	0.6002	likely_pathogenic	0.5623	ambiguous	-0.257	Destabilizing	0.97	D	0.513	neutral	None	None	None	None	N
K/E	0.1603	likely_benign	0.1461	benign	-0.239	Destabilizing	0.961	D	0.499	neutral	N	0.455694839	None	None	N
K/F	0.8292	likely_pathogenic	0.7948	pathogenic	-0.249	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
K/G	0.5305	ambiguous	0.4929	ambiguous	-0.167	Destabilizing	0.97	D	0.531	neutral	None	None	None	None	N
K/H	0.442	ambiguous	0.4017	ambiguous	-0.258	Destabilizing	1.0	D	0.499	neutral	None	None	None	None	N
K/I	0.3939	ambiguous	0.3465	ambiguous	0.37	Stabilizing	0.996	D	0.616	neutral	None	None	None	None	N
K/L	0.3884	ambiguous	0.3533	ambiguous	0.37	Stabilizing	0.985	D	0.525	neutral	None	None	None	None	N
K/M	0.2678	likely_benign	0.2422	benign	-0.14	Destabilizing	1.0	D	0.5	neutral	N	0.503902851	None	None	N
K/N	0.4549	ambiguous	0.3976	ambiguous	-0.047	Destabilizing	0.961	D	0.444	neutral	N	0.505006151	None	None	N
K/P	0.6843	likely_pathogenic	0.745	pathogenic	0.272	Stabilizing	0.996	D	0.452	neutral	None	None	None	None	N
K/Q	0.1527	likely_benign	0.1384	benign	-0.129	Destabilizing	0.994	D	0.425	neutral	N	0.491058206	None	None	N
K/R	0.0973	likely_benign	0.0949	benign	-0.074	Destabilizing	0.98	D	0.431	neutral	N	0.489095336	None	None	N
K/S	0.4633	ambiguous	0.4136	ambiguous	-0.391	Destabilizing	0.348	N	0.211	neutral	None	None	None	None	N
K/T	0.2019	likely_benign	0.1819	benign	-0.239	Destabilizing	0.925	D	0.527	neutral	N	0.476782187	None	None	N
K/V	0.383	ambiguous	0.3413	ambiguous	0.272	Stabilizing	0.996	D	0.477	neutral	None	None	None	None	N
K/W	0.8154	likely_pathogenic	0.7953	pathogenic	-0.367	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
K/Y	0.7375	likely_pathogenic	0.7033	pathogenic	-0.012	Destabilizing	0.999	D	0.578	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.