TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22270	67033;67034;67035	chr2:178580571;178580570;178580569	chr2:179445298;179445297;179445296
N2AB	20629	62110;62111;62112	chr2:178580571;178580570;178580569	chr2:179445298;179445297;179445296
N2A	19702	59329;59330;59331	chr2:178580571;178580570;178580569	chr2:179445298;179445297;179445296
N2B	13205	39838;39839;39840	chr2:178580571;178580570;178580569	chr2:179445298;179445297;179445296
Novex-1	13330	40213;40214;40215	chr2:178580571;178580570;178580569	chr2:179445298;179445297;179445296
Novex-2	13397	40414;40415;40416	chr2:178580571;178580570;178580569	chr2:179445298;179445297;179445296
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-126
• Domain position: 6
• Structural Position: 11
• Q(SASA): 0.482
• Predicted PPI site: I

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
T/I	rs2047465405	None	0.166	N	0.323	0.107	0.233150807113	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs2047465405	None	0.166	N	0.323	0.107	0.233150807113	gnomAD-4.0.0	6.57514E-06	None	None	None	None	I	None	2.41278E-05	0	None	0	0	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
T/A	0.1495	likely_benign	0.1576	benign	-0.612	Destabilizing	None	N	0.115	neutral	N	0.480989488	None	None	I
T/C	0.5891	likely_pathogenic	0.6181	pathogenic	-0.431	Destabilizing	0.965	D	0.369	neutral	None	None	None	None	I
T/D	0.8072	likely_pathogenic	0.8242	pathogenic	0.636	Stabilizing	0.722	D	0.457	neutral	None	None	None	None	I
T/E	0.6729	likely_pathogenic	0.7018	pathogenic	0.618	Stabilizing	0.561	D	0.393	neutral	None	None	None	None	I
T/F	0.561	ambiguous	0.6116	pathogenic	-0.834	Destabilizing	0.561	D	0.517	neutral	None	None	None	None	I
T/G	0.4241	ambiguous	0.447	ambiguous	-0.818	Destabilizing	0.209	N	0.33	neutral	None	None	None	None	I
T/H	0.6032	likely_pathogenic	0.621	pathogenic	-1.057	Destabilizing	0.965	D	0.396	neutral	None	None	None	None	I
T/I	0.2648	likely_benign	0.2959	benign	-0.171	Destabilizing	0.166	N	0.323	neutral	N	0.464984504	None	None	I
T/K	0.6937	likely_pathogenic	0.7041	pathogenic	-0.324	Destabilizing	0.491	N	0.385	neutral	N	0.493302638	None	None	I
T/L	0.1968	likely_benign	0.2197	benign	-0.171	Destabilizing	0.001	N	0.147	neutral	None	None	None	None	I
T/M	0.1326	likely_benign	0.1491	benign	-0.1	Destabilizing	0.818	D	0.39	neutral	None	None	None	None	I
T/N	0.2191	likely_benign	0.2315	benign	-0.233	Destabilizing	0.722	D	0.349	neutral	None	None	None	None	I
T/P	0.3	likely_benign	0.3001	benign	-0.286	Destabilizing	0.662	D	0.459	neutral	N	0.494764075	None	None	I
T/Q	0.503	ambiguous	0.5297	ambiguous	-0.358	Destabilizing	0.901	D	0.447	neutral	None	None	None	None	I
T/R	0.6755	likely_pathogenic	0.6886	pathogenic	-0.199	Destabilizing	0.662	D	0.485	neutral	N	0.499844608	None	None	I
T/S	0.2122	likely_benign	0.2177	benign	-0.588	Destabilizing	0.166	N	0.296	neutral	N	0.502439409	None	None	I
T/V	0.1747	likely_benign	0.1895	benign	-0.286	Destabilizing	0.001	N	0.115	neutral	None	None	None	None	I
T/W	0.8964	likely_pathogenic	0.9096	pathogenic	-0.767	Destabilizing	0.991	D	0.402	neutral	None	None	None	None	I
T/Y	0.5442	ambiguous	0.5835	pathogenic	-0.504	Destabilizing	0.901	D	0.489	neutral	None	None	None	None	I

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.