TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7492	22699;22700;22701	chr2:178722313;178722312;178722311	chr2:179587040;179587039;179587038
N2AB	7175	21748;21749;21750	chr2:178722313;178722312;178722311	chr2:179587040;179587039;179587038
N2A	6248	18967;18968;18969	chr2:178722313;178722312;178722311	chr2:179587040;179587039;179587038
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-59
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.2065
• 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/L	rs745460696	0.095	0.816	N	0.542	0.239	0.589461000006	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.02E-06	0
S/L	rs745460696	0.095	0.816	N	0.542	0.239	0.589461000006	gnomAD-4.0.0	2.05522E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70071E-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	0.0903	likely_benign	0.0889	benign	-1.095	Destabilizing	0.037	N	0.363	neutral	N	0.521898401	None	None	N
S/C	0.1642	likely_benign	0.1474	benign	-0.534	Destabilizing	0.994	D	0.555	neutral	None	None	None	None	N
S/D	0.4959	ambiguous	0.4428	ambiguous	-0.158	Destabilizing	0.884	D	0.479	neutral	None	None	None	None	N
S/E	0.5026	ambiguous	0.4411	ambiguous	-0.055	Destabilizing	0.815	D	0.442	neutral	None	None	None	None	N
S/F	0.1684	likely_benign	0.1497	benign	-1.144	Destabilizing	0.995	D	0.609	neutral	None	None	None	None	N
S/G	0.154	likely_benign	0.1548	benign	-1.417	Destabilizing	0.853	D	0.434	neutral	None	None	None	None	N
S/H	0.3055	likely_benign	0.271	benign	-1.635	Destabilizing	0.998	D	0.555	neutral	None	None	None	None	N
S/I	0.1299	likely_benign	0.1218	benign	-0.301	Destabilizing	0.855	D	0.534	neutral	None	None	None	None	N
S/K	0.6198	likely_pathogenic	0.5691	pathogenic	-0.102	Destabilizing	0.855	D	0.408	neutral	None	None	None	None	N
S/L	0.0966	likely_benign	0.0951	benign	-0.301	Destabilizing	0.816	D	0.542	neutral	N	0.479051701	None	None	N
S/M	0.1767	likely_benign	0.17	benign	-0.146	Destabilizing	0.995	D	0.566	neutral	None	None	None	None	N
S/N	0.1636	likely_benign	0.1572	benign	-0.351	Destabilizing	0.472	N	0.477	neutral	None	None	None	None	N
S/P	0.932	likely_pathogenic	0.9307	pathogenic	-0.534	Destabilizing	0.921	D	0.541	neutral	N	0.506545743	None	None	N
S/Q	0.4358	ambiguous	0.3839	ambiguous	-0.343	Destabilizing	0.966	D	0.523	neutral	None	None	None	None	N
S/R	0.4906	ambiguous	0.4401	ambiguous	-0.252	Destabilizing	0.036	N	0.346	neutral	None	None	None	None	N
S/T	0.0646	likely_benign	0.0639	benign	-0.375	Destabilizing	0.001	N	0.189	neutral	N	0.404225868	None	None	N
S/V	0.1458	likely_benign	0.1391	benign	-0.534	Destabilizing	0.02	N	0.485	neutral	None	None	None	None	N
S/W	0.3612	ambiguous	0.3205	benign	-1.09	Destabilizing	1.0	D	0.622	neutral	None	None	None	None	N
S/Y	0.177	likely_benign	0.1612	benign	-0.776	Destabilizing	0.998	D	0.613	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.