TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	959	3100;3101;3102	chr2:178783031;178783030;178783029	chr2:179647758;179647757;179647756
N2AB	959	3100;3101;3102	chr2:178783031;178783030;178783029	chr2:179647758;179647757;179647756
N2A	959	3100;3101;3102	chr2:178783031;178783030;178783029	chr2:179647758;179647757;179647756
N2B	913	2962;2963;2964	chr2:178783031;178783030;178783029	chr2:179647758;179647757;179647756
Novex-1	913	2962;2963;2964	chr2:178783031;178783030;178783029	chr2:179647758;179647757;179647756
Novex-2	913	2962;2963;2964	chr2:178783031;178783030;178783029	chr2:179647758;179647757;179647756
Novex-3	959	3100;3101;3102	chr2:178783031;178783030;178783029	chr2:179647758;179647757;179647756

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-3
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.4794
• 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/Y	None	None	1.0	D	0.861	0.505	0.673716824456	gnomAD-4.0.0	1.59062E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8567E-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	0.1278	likely_benign	0.1412	benign	-0.416	Destabilizing	0.997	D	0.443	neutral	N	0.485036258	None	None	N
S/C	0.3917	ambiguous	0.4358	ambiguous	-0.326	Destabilizing	1.0	D	0.785	deleterious	D	0.522536008	None	None	N
S/D	0.737	likely_pathogenic	0.827	pathogenic	0.035	Stabilizing	0.999	D	0.675	neutral	None	None	None	None	N
S/E	0.8012	likely_pathogenic	0.8724	pathogenic	-0.024	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
S/F	0.6092	likely_pathogenic	0.7026	pathogenic	-0.776	Destabilizing	1.0	D	0.859	deleterious	N	0.518616875	None	None	N
S/G	0.2431	likely_benign	0.291	benign	-0.598	Destabilizing	0.999	D	0.487	neutral	None	None	None	None	N
S/H	0.7131	likely_pathogenic	0.7817	pathogenic	-1.098	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
S/I	0.5319	ambiguous	0.6341	pathogenic	-0.058	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
S/K	0.9082	likely_pathogenic	0.9484	pathogenic	-0.619	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
S/L	0.3041	likely_benign	0.3864	ambiguous	-0.058	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
S/M	0.4047	ambiguous	0.47	ambiguous	0.16	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
S/N	0.2968	likely_benign	0.3778	ambiguous	-0.402	Destabilizing	0.999	D	0.626	neutral	None	None	None	None	N
S/P	0.4251	ambiguous	0.5341	ambiguous	-0.144	Destabilizing	1.0	D	0.819	deleterious	N	0.446240953	None	None	N
S/Q	0.7757	likely_pathogenic	0.8397	pathogenic	-0.614	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
S/R	0.8691	likely_pathogenic	0.9251	pathogenic	-0.433	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
S/T	0.1436	likely_benign	0.1722	benign	-0.469	Destabilizing	0.999	D	0.448	neutral	N	0.472262155	None	None	N
S/V	0.4856	ambiguous	0.5676	pathogenic	-0.144	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
S/W	0.7341	likely_pathogenic	0.8072	pathogenic	-0.771	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
S/Y	0.5272	ambiguous	0.6164	pathogenic	-0.506	Destabilizing	1.0	D	0.861	deleterious	D	0.571370817	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.