TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2763	8512;8513;8514	chr2:178770505;178770504;178770503	chr2:179635232;179635231;179635230
N2AB	2763	8512;8513;8514	chr2:178770505;178770504;178770503	chr2:179635232;179635231;179635230
N2A	2763	8512;8513;8514	chr2:178770505;178770504;178770503	chr2:179635232;179635231;179635230
N2B	2717	8374;8375;8376	chr2:178770505;178770504;178770503	chr2:179635232;179635231;179635230
Novex-1	2717	8374;8375;8376	chr2:178770505;178770504;178770503	chr2:179635232;179635231;179635230
Novex-2	2717	8374;8375;8376	chr2:178770505;178770504;178770503	chr2:179635232;179635231;179635230
Novex-3	2763	8512;8513;8514	chr2:178770505;178770504;178770503	chr2:179635232;179635231;179635230

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-17
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.2188
• 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/F	rs1231235466	None	0.093	N	0.615	0.356	0.684933780128	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	6.07533E-05	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	0.098	likely_benign	0.1011	benign	-0.815	Destabilizing	0.005	N	0.406	neutral	D	0.5782874	None	None	N
S/C	0.1101	likely_benign	0.1356	benign	-0.474	Destabilizing	0.612	D	0.607	neutral	D	0.541227067	None	None	N
S/D	0.356	ambiguous	0.3724	ambiguous	-0.863	Destabilizing	0.072	N	0.554	neutral	None	None	None	None	N
S/E	0.356	ambiguous	0.3611	ambiguous	-0.674	Destabilizing	0.072	N	0.555	neutral	None	None	None	None	N
S/F	0.2022	likely_benign	0.2101	benign	-0.716	Destabilizing	0.093	N	0.615	neutral	N	0.512905716	None	None	N
S/G	0.1282	likely_benign	0.1482	benign	-1.219	Destabilizing	0.031	N	0.541	neutral	None	None	None	None	N
S/H	0.2338	likely_benign	0.2179	benign	-1.525	Destabilizing	0.001	N	0.445	neutral	None	None	None	None	N
S/I	0.1568	likely_benign	0.1693	benign	0.21	Stabilizing	0.038	N	0.591	neutral	None	None	None	None	N
S/K	0.5276	ambiguous	0.5187	ambiguous	-0.003	Destabilizing	0.072	N	0.561	neutral	None	None	None	None	N
S/L	0.1138	likely_benign	0.123	benign	0.21	Stabilizing	None	N	0.487	neutral	None	None	None	None	N
S/M	0.1807	likely_benign	0.1589	benign	0.126	Stabilizing	0.12	N	0.613	neutral	None	None	None	None	N
S/N	0.1266	likely_benign	0.124	benign	-0.641	Destabilizing	0.072	N	0.577	neutral	None	None	None	None	N
S/P	0.8811	likely_pathogenic	0.9193	pathogenic	-0.096	Destabilizing	0.295	N	0.608	neutral	D	0.581772319	None	None	N
S/Q	0.3686	ambiguous	0.353	ambiguous	-0.413	Destabilizing	0.214	N	0.607	neutral	None	None	None	None	N
S/R	0.4349	ambiguous	0.4334	ambiguous	-0.416	Destabilizing	0.072	N	0.595	neutral	None	None	None	None	N
S/T	0.0657	likely_benign	0.0597	benign	-0.396	Destabilizing	None	N	0.254	neutral	N	0.432277111	None	None	N
S/V	0.1717	likely_benign	0.1826	benign	-0.096	Destabilizing	0.016	N	0.561	neutral	None	None	None	None	N
S/W	0.3203	likely_benign	0.334	benign	-0.882	Destabilizing	0.864	D	0.677	prob.neutral	None	None	None	None	N
S/Y	0.1591	likely_benign	0.1715	benign	-0.438	Destabilizing	0.171	N	0.613	neutral	D	0.581772319	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.