TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21519	64780;64781;64782	chr2:178585189;178585188;178585187	chr2:179449916;179449915;179449914
N2AB	19878	59857;59858;59859	chr2:178585189;178585188;178585187	chr2:179449916;179449915;179449914
N2A	18951	57076;57077;57078	chr2:178585189;178585188;178585187	chr2:179449916;179449915;179449914
N2B	12454	37585;37586;37587	chr2:178585189;178585188;178585187	chr2:179449916;179449915;179449914
Novex-1	12579	37960;37961;37962	chr2:178585189;178585188;178585187	chr2:179449916;179449915;179449914
Novex-2	12646	38161;38162;38163	chr2:178585189;178585188;178585187	chr2:179449916;179449915;179449914
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-124
• Domain position: 51
• Structural Position: 131
• Q(SASA): 0.4585
• 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
D/E	rs1336928920	-0.415	None	N	0.098	0.06	0.0954503805726	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
D/E	rs1336928920	-0.415	None	N	0.098	0.06	0.0954503805726	gnomAD-4.0.0	6.84384E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99687E-07	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
D/A	0.1018	likely_benign	0.0997	benign	0.09	Stabilizing	0.012	N	0.23	neutral	N	0.457152623	None	None	N
D/C	0.4887	ambiguous	0.4864	ambiguous	0.133	Stabilizing	0.864	D	0.351	neutral	None	None	None	None	N
D/E	0.0873	likely_benign	0.0929	benign	-0.113	Destabilizing	None	N	0.098	neutral	N	0.43600656	None	None	N
D/F	0.4494	ambiguous	0.4363	ambiguous	-0.147	Destabilizing	0.214	N	0.381	neutral	None	None	None	None	N
D/G	0.1068	likely_benign	0.1058	benign	-0.007	Destabilizing	None	N	0.171	neutral	N	0.378128905	None	None	N
D/H	0.2267	likely_benign	0.2087	benign	0.317	Stabilizing	0.295	N	0.32	neutral	N	0.487302172	None	None	N
D/I	0.2179	likely_benign	0.2136	benign	0.273	Stabilizing	0.038	N	0.381	neutral	None	None	None	None	N
D/K	0.2041	likely_benign	0.1982	benign	0.495	Stabilizing	0.016	N	0.267	neutral	None	None	None	None	N
D/L	0.2377	likely_benign	0.2282	benign	0.273	Stabilizing	None	N	0.196	neutral	None	None	None	None	N
D/M	0.3887	ambiguous	0.3837	ambiguous	0.189	Stabilizing	0.214	N	0.355	neutral	None	None	None	None	N
D/N	0.0878	likely_benign	0.0842	benign	0.507	Stabilizing	0.055	N	0.144	neutral	N	0.454939037	None	None	N
D/P	0.2551	likely_benign	0.2659	benign	0.231	Stabilizing	None	N	0.19	neutral	None	None	None	None	N
D/Q	0.1848	likely_benign	0.1771	benign	0.481	Stabilizing	0.001	N	0.121	neutral	None	None	None	None	N
D/R	0.2601	likely_benign	0.2485	benign	0.615	Stabilizing	0.038	N	0.367	neutral	None	None	None	None	N
D/S	0.0941	likely_benign	0.0882	benign	0.351	Stabilizing	0.003	N	0.133	neutral	None	None	None	None	N
D/T	0.153	likely_benign	0.1449	benign	0.423	Stabilizing	0.038	N	0.266	neutral	None	None	None	None	N
D/V	0.1416	likely_benign	0.1391	benign	0.231	Stabilizing	0.029	N	0.293	neutral	N	0.469063128	None	None	N
D/W	0.7808	likely_pathogenic	0.7726	pathogenic	-0.16	Destabilizing	0.864	D	0.367	neutral	None	None	None	None	N
D/Y	0.2287	likely_benign	0.2126	benign	0.068	Stabilizing	0.56	D	0.379	neutral	N	0.454188085	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.