TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20396	61411;61412;61413	chr2:178590539;178590538;178590537	chr2:179455266;179455265;179455264
N2AB	18755	56488;56489;56490	chr2:178590539;178590538;178590537	chr2:179455266;179455265;179455264
N2A	17828	53707;53708;53709	chr2:178590539;178590538;178590537	chr2:179455266;179455265;179455264
N2B	11331	34216;34217;34218	chr2:178590539;178590538;178590537	chr2:179455266;179455265;179455264
Novex-1	11456	34591;34592;34593	chr2:178590539;178590538;178590537	chr2:179455266;179455265;179455264
Novex-2	11523	34792;34793;34794	chr2:178590539;178590538;178590537	chr2:179455266;179455265;179455264
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-36
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.992
• 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
L/P	None	None	0.966	N	0.315	0.294	0.629339664297	gnomAD-4.0.0	2.73823E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59914E-06	0	0
L/R	rs2049986459	None	0.934	N	0.323	0.216	0.57330664977	gnomAD-4.0.0	1.36912E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79957E-06	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
L/A	0.2213	likely_benign	0.1769	benign	-0.522	Destabilizing	0.525	D	0.324	neutral	None	None	None	None	I
L/C	0.5988	likely_pathogenic	0.5552	ambiguous	-0.857	Destabilizing	0.998	D	0.275	neutral	None	None	None	None	I
L/D	0.7141	likely_pathogenic	0.6541	pathogenic	-0.197	Destabilizing	0.728	D	0.336	neutral	None	None	None	None	I
L/E	0.482	ambiguous	0.4139	ambiguous	-0.274	Destabilizing	0.842	D	0.337	neutral	None	None	None	None	I
L/F	0.235	likely_benign	0.1873	benign	-0.591	Destabilizing	0.989	D	0.299	neutral	N	0.46599996	None	None	I
L/G	0.545	ambiguous	0.4788	ambiguous	-0.639	Destabilizing	0.728	D	0.336	neutral	None	None	None	None	I
L/H	0.3362	likely_benign	0.2998	benign	0.086	Stabilizing	0.966	D	0.255	neutral	N	0.496874166	None	None	I
L/I	0.1028	likely_benign	0.0908	benign	-0.326	Destabilizing	0.801	D	0.319	neutral	N	0.440116806	None	None	I
L/K	0.3828	ambiguous	0.3624	ambiguous	-0.374	Destabilizing	0.842	D	0.34	neutral	None	None	None	None	I
L/M	0.1334	likely_benign	0.1214	benign	-0.667	Destabilizing	0.991	D	0.316	neutral	None	None	None	None	I
L/N	0.3095	likely_benign	0.2468	benign	-0.283	Destabilizing	0.007	N	0.216	neutral	None	None	None	None	I
L/P	0.2993	likely_benign	0.2769	benign	-0.364	Destabilizing	0.966	D	0.315	neutral	N	0.476901538	None	None	I
L/Q	0.2077	likely_benign	0.1828	benign	-0.434	Destabilizing	0.974	D	0.327	neutral	None	None	None	None	I
L/R	0.3401	ambiguous	0.3335	benign	0.085	Stabilizing	0.934	D	0.323	neutral	N	0.425184639	None	None	I
L/S	0.2866	likely_benign	0.2171	benign	-0.689	Destabilizing	0.172	N	0.236	neutral	None	None	None	None	I
L/T	0.2584	likely_benign	0.1995	benign	-0.661	Destabilizing	0.029	N	0.155	neutral	None	None	None	None	I
L/V	0.1031	likely_benign	0.0908	benign	-0.364	Destabilizing	0.625	D	0.306	neutral	N	0.457105056	None	None	I
L/W	0.4487	ambiguous	0.4188	ambiguous	-0.6	Destabilizing	0.998	D	0.325	neutral	None	None	None	None	I
L/Y	0.4487	ambiguous	0.3899	ambiguous	-0.38	Destabilizing	0.991	D	0.293	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.