TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7897	23914;23915;23916	chr2:178719803;178719802;178719801	chr2:179584530;179584529;179584528
N2AB	7580	22963;22964;22965	chr2:178719803;178719802;178719801	chr2:179584530;179584529;179584528
N2A	6653	20182;20183;20184	chr2:178719803;178719802;178719801	chr2:179584530;179584529;179584528
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-64
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.2747
• 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	rs1276562007	None	0.852	N	0.456	0.21	0.107399877778	gnomAD-4.0.0	1.59651E-06	None	None	None	None	N	None	0	0	None	0	2.77747E-05	None	0	0	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
P/A	0.0777	likely_benign	0.0702	benign	-0.548	Destabilizing	0.134	N	0.243	neutral	N	0.493822713	None	None	N
P/C	0.5975	likely_pathogenic	0.4945	ambiguous	-0.597	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
P/D	0.3344	likely_benign	0.2647	benign	-0.623	Destabilizing	0.884	D	0.469	neutral	None	None	None	None	N
P/E	0.2436	likely_benign	0.2036	benign	-0.74	Destabilizing	0.939	D	0.465	neutral	None	None	None	None	N
P/F	0.5167	ambiguous	0.416	ambiguous	-0.773	Destabilizing	0.991	D	0.594	neutral	None	None	None	None	N
P/G	0.3286	likely_benign	0.2625	benign	-0.681	Destabilizing	0.939	D	0.505	neutral	None	None	None	None	N
P/H	0.219	likely_benign	0.1748	benign	-0.252	Destabilizing	0.997	D	0.572	neutral	N	0.461047712	None	None	N
P/I	0.3531	ambiguous	0.2957	benign	-0.345	Destabilizing	0.884	D	0.549	neutral	None	None	None	None	N
P/K	0.3205	likely_benign	0.2539	benign	-0.591	Destabilizing	0.939	D	0.462	neutral	None	None	None	None	N
P/L	0.1406	likely_benign	0.124	benign	-0.345	Destabilizing	0.852	D	0.513	neutral	N	0.514467344	None	None	N
P/M	0.3153	likely_benign	0.2665	benign	-0.396	Destabilizing	0.991	D	0.574	neutral	None	None	None	None	N
P/N	0.3049	likely_benign	0.2318	benign	-0.286	Destabilizing	0.17	N	0.379	neutral	None	None	None	None	N
P/Q	0.1691	likely_benign	0.1388	benign	-0.561	Destabilizing	0.991	D	0.551	neutral	None	None	None	None	N
P/R	0.2171	likely_benign	0.1726	benign	-0.014	Destabilizing	0.988	D	0.587	neutral	N	0.462515742	None	None	N
P/S	0.1233	likely_benign	0.0993	benign	-0.588	Destabilizing	0.852	D	0.456	neutral	N	0.398813609	None	None	N
P/T	0.1127	likely_benign	0.0955	benign	-0.612	Destabilizing	0.92	D	0.451	neutral	N	0.510637605	None	None	N
P/V	0.2367	likely_benign	0.2006	benign	-0.378	Destabilizing	0.17	N	0.4	neutral	None	None	None	None	N
P/W	0.6956	likely_pathogenic	0.5857	pathogenic	-0.853	Destabilizing	0.999	D	0.644	neutral	None	None	None	None	N
P/Y	0.471	ambiguous	0.3753	ambiguous	-0.567	Destabilizing	0.997	D	0.594	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.