TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7960	24103;24104;24105	chr2:178719614;178719613;178719612	chr2:179584341;179584340;179584339
N2AB	7643	23152;23153;23154	chr2:178719614;178719613;178719612	chr2:179584341;179584340;179584339
N2A	6716	20371;20372;20373	chr2:178719614;178719613;178719612	chr2:179584341;179584340;179584339
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-64
• Domain position: 72
• Structural Position: 155
• Q(SASA): 0.1681
• 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/N	rs369302142	0.177	0.055	N	0.555	0.175	None	gnomAD-2.1.1	3.62E-05	None	None	None	None	N	None	0	8.7E-05	None	1.99164E-04	0	None	0	None	0	2.67E-05	1.66223E-04
S/N	rs369302142	0.177	0.055	N	0.555	0.175	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	2.88351E-04	0	None	0	0	0	0	4.78927E-04
S/N	rs369302142	0.177	0.055	N	0.555	0.175	None	gnomAD-4.0.0	1.7356E-05	None	None	None	None	N	None	0	1.00037E-04	None	3.38043E-04	0	None	0	0	6.78252E-06	0	6.40718E-05

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	0.1073	likely_benign	0.1103	benign	-0.698	Destabilizing	0.007	N	0.407	neutral	None	None	None	None	N
S/C	0.1255	likely_benign	0.1394	benign	-0.132	Destabilizing	0.612	D	0.629	neutral	N	0.472012397	None	None	N
S/D	0.5271	ambiguous	0.5147	ambiguous	-0.895	Destabilizing	0.072	N	0.544	neutral	None	None	None	None	N
S/E	0.611	likely_pathogenic	0.6187	pathogenic	-0.654	Destabilizing	0.072	N	0.55	neutral	None	None	None	None	N
S/F	0.2203	likely_benign	0.2418	benign	-0.618	Destabilizing	0.356	N	0.612	neutral	None	None	None	None	N
S/G	0.1305	likely_benign	0.1326	benign	-1.122	Destabilizing	None	N	0.293	neutral	N	0.471758907	None	None	N
S/H	0.3239	likely_benign	0.3278	benign	-1.326	Destabilizing	0.628	D	0.629	neutral	None	None	None	None	N
S/I	0.1951	likely_benign	0.2024	benign	0.406	Stabilizing	0.001	N	0.603	neutral	N	0.486203307	None	None	N
S/K	0.7232	likely_pathogenic	0.7362	pathogenic	0.608	Stabilizing	0.072	N	0.547	neutral	None	None	None	None	N
S/L	0.1254	likely_benign	0.1335	benign	0.406	Stabilizing	0.016	N	0.601	neutral	None	None	None	None	N
S/M	0.2425	likely_benign	0.2489	benign	0.215	Stabilizing	0.356	N	0.625	neutral	None	None	None	None	N
S/N	0.182	likely_benign	0.1752	benign	-0.21	Destabilizing	0.055	N	0.555	neutral	N	0.471758907	None	None	N
S/P	0.963	likely_pathogenic	0.9608	pathogenic	0.072	Stabilizing	0.356	N	0.63	neutral	None	None	None	None	N
S/Q	0.5335	ambiguous	0.5446	ambiguous	0.109	Stabilizing	0.356	N	0.585	neutral	None	None	None	None	N
S/R	0.5543	ambiguous	0.5477	ambiguous	0.017	Stabilizing	0.171	N	0.631	neutral	N	0.482450926	None	None	N
S/T	0.0699	likely_benign	0.0753	benign	0.089	Stabilizing	None	N	0.242	neutral	N	0.372395012	None	None	N
S/V	0.2167	likely_benign	0.2287	benign	0.072	Stabilizing	0.001	N	0.527	neutral	None	None	None	None	N
S/W	0.3737	ambiguous	0.386	ambiguous	-0.833	Destabilizing	0.864	D	0.713	prob.delet.	None	None	None	None	N
S/Y	0.1883	likely_benign	0.1978	benign	-0.331	Destabilizing	0.356	N	0.611	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.