TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22298	67117;67118;67119	chr2:178580487;178580486;178580485	chr2:179445214;179445213;179445212
N2AB	20657	62194;62195;62196	chr2:178580487;178580486;178580485	chr2:179445214;179445213;179445212
N2A	19730	59413;59414;59415	chr2:178580487;178580486;178580485	chr2:179445214;179445213;179445212
N2B	13233	39922;39923;39924	chr2:178580487;178580486;178580485	chr2:179445214;179445213;179445212
Novex-1	13358	40297;40298;40299	chr2:178580487;178580486;178580485	chr2:179445214;179445213;179445212
Novex-2	13425	40498;40499;40500	chr2:178580487;178580486;178580485	chr2:179445214;179445213;179445212
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-126
• Domain position: 34
• Structural Position: 51
• Q(SASA): 0.429
• 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
P/S	rs72646871	-0.79	0.101	N	0.383	0.038	0.0920862733494	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	1.665E-04
P/S	rs72646871	-0.79	0.101	N	0.383	0.038	0.0920862733494	gnomAD-4.0.0	4.77931E-06	None	None	None	None	N	None	0	2.28833E-05	None	0	0	None	0	0	2.86116E-06	0	3.02939E-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
P/A	0.1293	likely_benign	0.1171	benign	-0.474	Destabilizing	0.047	N	0.324	neutral	N	0.397949604	None	None	N
P/C	0.7182	likely_pathogenic	0.6634	pathogenic	-0.753	Destabilizing	0.94	D	0.427	neutral	None	None	None	None	N
P/D	0.4992	ambiguous	0.4201	ambiguous	-0.255	Destabilizing	0.418	N	0.436	neutral	None	None	None	None	N
P/E	0.2982	likely_benign	0.2623	benign	-0.352	Destabilizing	0.129	N	0.381	neutral	None	None	None	None	N
P/F	0.7152	likely_pathogenic	0.6599	pathogenic	-0.613	Destabilizing	0.418	N	0.531	neutral	None	None	None	None	N
P/G	0.3657	ambiguous	0.3361	benign	-0.612	Destabilizing	0.418	N	0.428	neutral	None	None	None	None	N
P/H	0.3913	ambiguous	0.3286	benign	-0.115	Destabilizing	0.716	D	0.427	neutral	None	None	None	None	N
P/I	0.3786	ambiguous	0.3505	ambiguous	-0.253	Destabilizing	0.129	N	0.4	neutral	None	None	None	None	N
P/K	0.4504	ambiguous	0.3882	ambiguous	-0.508	Destabilizing	0.129	N	0.387	neutral	None	None	None	None	N
P/L	0.1951	likely_benign	0.1709	benign	-0.253	Destabilizing	0.001	N	0.191	neutral	N	0.41911431	None	None	N
P/M	0.3348	likely_benign	0.3129	benign	-0.463	Destabilizing	0.027	N	0.295	neutral	None	None	None	None	N
P/N	0.3692	ambiguous	0.3264	benign	-0.306	Destabilizing	0.418	N	0.493	neutral	None	None	None	None	N
P/Q	0.2275	likely_benign	0.2001	benign	-0.511	Destabilizing	0.007	N	0.264	neutral	N	0.398122962	None	None	N
P/R	0.4031	ambiguous	0.341	ambiguous	-0.012	Destabilizing	0.213	N	0.514	neutral	N	0.441316379	None	None	N
P/S	0.2115	likely_benign	0.183	benign	-0.678	Destabilizing	0.101	N	0.383	neutral	N	0.440969663	None	None	N
P/T	0.1559	likely_benign	0.1412	benign	-0.672	Destabilizing	0.183	N	0.393	neutral	N	0.427925794	None	None	N
P/V	0.2516	likely_benign	0.2351	benign	-0.293	Destabilizing	None	N	0.167	neutral	None	None	None	None	N
P/W	0.8243	likely_pathogenic	0.7767	pathogenic	-0.696	Destabilizing	0.983	D	0.429	neutral	None	None	None	None	N
P/Y	0.6239	likely_pathogenic	0.5593	ambiguous	-0.407	Destabilizing	0.836	D	0.516	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.