TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16314	49165;49166;49167	chr2:178614574;178614573;178614572	chr2:179479301;179479300;179479299
N2AB	14673	44242;44243;44244	chr2:178614574;178614573;178614572	chr2:179479301;179479300;179479299
N2A	13746	41461;41462;41463	chr2:178614574;178614573;178614572	chr2:179479301;179479300;179479299
N2B	7249	21970;21971;21972	chr2:178614574;178614573;178614572	chr2:179479301;179479300;179479299
Novex-1	7374	22345;22346;22347	chr2:178614574;178614573;178614572	chr2:179479301;179479300;179479299
Novex-2	7441	22546;22547;22548	chr2:178614574;178614573;178614572	chr2:179479301;179479300;179479299
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-110
• Domain position: 53
• Structural Position: 136
• Q(SASA): 0.1268
• 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	rs375909143	-0.354	1.0	N	0.867	0.438	None	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	6.47E-05	0	None	0	0	None	0	None	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
S/A	0.2186	likely_benign	0.2154	benign	-0.751	Destabilizing	0.997	D	0.618	neutral	N	0.437258266	None	None	N
S/C	0.2704	likely_benign	0.2898	benign	-0.5	Destabilizing	1.0	D	0.845	deleterious	N	0.48021072	None	None	N
S/D	0.9901	likely_pathogenic	0.9901	pathogenic	-1.28	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
S/E	0.9935	likely_pathogenic	0.9938	pathogenic	-1.073	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	N
S/F	0.9784	likely_pathogenic	0.9794	pathogenic	-0.653	Destabilizing	1.0	D	0.868	deleterious	N	0.513690021	None	None	N
S/G	0.5556	ambiguous	0.5348	ambiguous	-1.16	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
S/H	0.9749	likely_pathogenic	0.9751	pathogenic	-1.572	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
S/I	0.8915	likely_pathogenic	0.8892	pathogenic	0.295	Stabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
S/K	0.9989	likely_pathogenic	0.9987	pathogenic	-0.017	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
S/L	0.7916	likely_pathogenic	0.7816	pathogenic	0.295	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
S/M	0.7904	likely_pathogenic	0.7805	pathogenic	0.223	Stabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
S/N	0.8777	likely_pathogenic	0.9002	pathogenic	-0.773	Destabilizing	0.999	D	0.666	neutral	None	None	None	None	N
S/P	0.9973	likely_pathogenic	0.9973	pathogenic	-0.018	Destabilizing	1.0	D	0.845	deleterious	D	0.525855123	None	None	N
S/Q	0.9863	likely_pathogenic	0.9861	pathogenic	-0.494	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
S/R	0.9985	likely_pathogenic	0.9982	pathogenic	-0.523	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
S/T	0.1772	likely_benign	0.1834	benign	-0.425	Destabilizing	0.999	D	0.625	neutral	N	0.451513831	None	None	N
S/V	0.7846	likely_pathogenic	0.786	pathogenic	-0.018	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
S/W	0.9861	likely_pathogenic	0.9846	pathogenic	-0.919	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
S/Y	0.957	likely_pathogenic	0.9558	pathogenic	-0.446	Destabilizing	1.0	D	0.867	deleterious	N	0.438003393	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.