TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22227	66904;66905;66906	chr2:178581589;178581588;178581587	chr2:179446316;179446315;179446314
N2AB	20586	61981;61982;61983	chr2:178581589;178581588;178581587	chr2:179446316;179446315;179446314
N2A	19659	59200;59201;59202	chr2:178581589;178581588;178581587	chr2:179446316;179446315;179446314
N2B	13162	39709;39710;39711	chr2:178581589;178581588;178581587	chr2:179446316;179446315;179446314
Novex-1	13287	40084;40085;40086	chr2:178581589;178581588;178581587	chr2:179446316;179446315;179446314
Novex-2	13354	40285;40286;40287	chr2:178581589;178581588;178581587	chr2:179446316;179446315;179446314
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Fn3-49
• Domain position: 72
• Structural Position: 103
• Q(SASA): 0.436
• 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
Q/P	rs1403005823	None	0.028	N	0.403	0.228	0.270001397563	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Q/P	rs1403005823	None	0.028	N	0.403	0.228	0.270001397563	gnomAD-4.0.0	6.57566E-06	None	None	None	None	N	None	2.41289E-05	0	None	0	0	None	0	0	0	0	0
Q/R	rs1403005823	None	0.007	N	0.265	0.219	0.130388298395	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
Q/R	rs1403005823	None	0.007	N	0.265	0.219	0.130388298395	gnomAD-4.0.0	6.57566E-06	None	None	None	None	N	None	2.41289E-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
Q/A	0.0951	likely_benign	0.1027	benign	-0.906	Destabilizing	0.004	N	0.253	neutral	None	None	None	None	N
Q/C	0.518	ambiguous	0.5276	ambiguous	-0.143	Destabilizing	0.788	D	0.508	neutral	None	None	None	None	N
Q/D	0.4126	ambiguous	0.3703	ambiguous	-0.825	Destabilizing	None	N	0.074	neutral	None	None	None	None	N
Q/E	0.0533	likely_benign	0.0491	benign	-0.641	Destabilizing	None	N	0.075	neutral	N	0.331562402	None	None	N
Q/F	0.6557	likely_pathogenic	0.6738	pathogenic	-0.292	Destabilizing	0.497	N	0.582	neutral	None	None	None	None	N
Q/G	0.2679	likely_benign	0.2679	benign	-1.334	Destabilizing	0.008	N	0.335	neutral	None	None	None	None	N
Q/H	0.2987	likely_benign	0.2829	benign	-0.908	Destabilizing	0.196	N	0.373	neutral	N	0.474768097	None	None	N
Q/I	0.2537	likely_benign	0.2646	benign	0.236	Stabilizing	0.085	N	0.6	neutral	None	None	None	None	N
Q/K	0.1015	likely_benign	0.1041	benign	-0.434	Destabilizing	0.003	N	0.167	neutral	N	0.428416945	None	None	N
Q/L	0.0928	likely_benign	0.0974	benign	0.236	Stabilizing	0.014	N	0.428	neutral	N	0.469668921	None	None	N
Q/M	0.2274	likely_benign	0.2443	benign	0.594	Stabilizing	0.497	N	0.34	neutral	None	None	None	None	N
Q/N	0.274	likely_benign	0.2815	benign	-1.057	Destabilizing	0.018	N	0.211	neutral	None	None	None	None	N
Q/P	0.0618	likely_benign	0.0615	benign	-0.115	Destabilizing	0.028	N	0.403	neutral	N	0.482867505	None	None	N
Q/R	0.1353	likely_benign	0.1374	benign	-0.444	Destabilizing	0.007	N	0.265	neutral	N	0.420741611	None	None	N
Q/S	0.1405	likely_benign	0.1564	benign	-1.296	Destabilizing	0.004	N	0.155	neutral	None	None	None	None	N
Q/T	0.1529	likely_benign	0.1514	benign	-0.907	Destabilizing	0.018	N	0.374	neutral	None	None	None	None	N
Q/V	0.1427	likely_benign	0.1478	benign	-0.115	Destabilizing	0.018	N	0.424	neutral	None	None	None	None	N
Q/W	0.6626	likely_pathogenic	0.6626	pathogenic	-0.166	Destabilizing	0.788	D	0.503	neutral	None	None	None	None	N
Q/Y	0.5223	ambiguous	0.5307	ambiguous	0.073	Stabilizing	0.22	N	0.517	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.