TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14628	44107;44108;44109	chr2:178631166;178631165;178631164	chr2:179495893;179495892;179495891
N2AB	12987	39184;39185;39186	chr2:178631166;178631165;178631164	chr2:179495893;179495892;179495891
N2A	12060	36403;36404;36405	chr2:178631166;178631165;178631164	chr2:179495893;179495892;179495891
N2B	5563	16912;16913;16914	chr2:178631166;178631165;178631164	chr2:179495893;179495892;179495891
Novex-1	5688	17287;17288;17289	chr2:178631166;178631165;178631164	chr2:179495893;179495892;179495891
Novex-2	5755	17488;17489;17490	chr2:178631166;178631165;178631164	chr2:179495893;179495892;179495891
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-97
• Domain position: 43
• Structural Position: 73
• Q(SASA): 0.3726
• 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
S/F	None	None	1.0	D	0.751	0.467	0.541692676538	gnomAD-4.0.0	1.59238E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85963E-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
S/A	0.1249	likely_benign	0.1197	benign	-0.181	Destabilizing	0.997	D	0.423	neutral	D	0.568880262	None	None	N
S/C	0.3067	likely_benign	0.2504	benign	-0.252	Destabilizing	1.0	D	0.706	prob.neutral	D	0.631784081	None	None	N
S/D	0.5039	ambiguous	0.5038	ambiguous	0.034	Stabilizing	0.999	D	0.571	neutral	None	None	None	None	N
S/E	0.7218	likely_pathogenic	0.7247	pathogenic	-0.072	Destabilizing	0.999	D	0.559	neutral	None	None	None	None	N
S/F	0.4762	ambiguous	0.4328	ambiguous	-0.851	Destabilizing	1.0	D	0.751	deleterious	D	0.717126165	None	None	N
S/G	0.1238	likely_benign	0.1177	benign	-0.259	Destabilizing	0.999	D	0.477	neutral	None	None	None	None	N
S/H	0.6638	likely_pathogenic	0.6307	pathogenic	-0.71	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
S/I	0.499	ambiguous	0.4638	ambiguous	-0.108	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
S/K	0.896	likely_pathogenic	0.8862	pathogenic	-0.466	Destabilizing	0.999	D	0.561	neutral	None	None	None	None	N
S/L	0.2247	likely_benign	0.1953	benign	-0.108	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
S/M	0.4777	ambiguous	0.4237	ambiguous	-0.005	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
S/N	0.2906	likely_benign	0.2665	benign	-0.159	Destabilizing	0.999	D	0.547	neutral	None	None	None	None	N
S/P	0.8195	likely_pathogenic	0.8246	pathogenic	-0.105	Destabilizing	1.0	D	0.663	neutral	D	0.595391099	None	None	N
S/Q	0.7753	likely_pathogenic	0.7638	pathogenic	-0.396	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	N
S/R	0.8533	likely_pathogenic	0.8388	pathogenic	-0.238	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
S/T	0.1342	likely_benign	0.1169	benign	-0.246	Destabilizing	0.999	D	0.449	neutral	D	0.530839557	None	None	N
S/V	0.4177	ambiguous	0.3813	ambiguous	-0.105	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
S/W	0.6828	likely_pathogenic	0.6298	pathogenic	-0.926	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
S/Y	0.484	ambiguous	0.4273	ambiguous	-0.621	Destabilizing	1.0	D	0.753	deleterious	D	0.68064343	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.