TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15817	47674;47675;47676	chr2:178617902;178617901;178617900	chr2:179482629;179482628;179482627
N2AB	14176	42751;42752;42753	chr2:178617902;178617901;178617900	chr2:179482629;179482628;179482627
N2A	13249	39970;39971;39972	chr2:178617902;178617901;178617900	chr2:179482629;179482628;179482627
N2B	6752	20479;20480;20481	chr2:178617902;178617901;178617900	chr2:179482629;179482628;179482627
Novex-1	6877	20854;20855;20856	chr2:178617902;178617901;178617900	chr2:179482629;179482628;179482627
Novex-2	6944	21055;21056;21057	chr2:178617902;178617901;178617900	chr2:179482629;179482628;179482627
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-2
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.2677
• 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/C	None	None	0.999	D	0.661	0.388	0.429780353351	gnomAD-4.0.0	1.59341E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88239E-05	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
S/A	0.071	likely_benign	0.073	benign	-0.668	Destabilizing	0.64	D	0.47	neutral	N	0.471360301	None	None	N
S/C	0.114	likely_benign	0.1074	benign	-0.425	Destabilizing	0.999	D	0.661	neutral	D	0.596482074	None	None	N
S/D	0.3351	likely_benign	0.3418	ambiguous	0.371	Stabilizing	0.919	D	0.447	neutral	None	None	None	None	N
S/E	0.2935	likely_benign	0.2971	benign	0.377	Stabilizing	0.851	D	0.436	neutral	None	None	None	None	N
S/F	0.1442	likely_benign	0.1396	benign	-0.976	Destabilizing	0.995	D	0.706	prob.neutral	D	0.548663539	None	None	N
S/G	0.1	likely_benign	0.1051	benign	-0.899	Destabilizing	0.034	N	0.283	neutral	None	None	None	None	N
S/H	0.1982	likely_benign	0.1927	benign	-1.248	Destabilizing	0.997	D	0.667	neutral	None	None	None	None	N
S/I	0.1376	likely_benign	0.1361	benign	-0.161	Destabilizing	0.996	D	0.691	prob.neutral	None	None	None	None	N
S/K	0.326	likely_benign	0.3158	benign	-0.327	Destabilizing	0.851	D	0.443	neutral	None	None	None	None	N
S/L	0.0951	likely_benign	0.091	benign	-0.161	Destabilizing	0.988	D	0.6	neutral	None	None	None	None	N
S/M	0.1562	likely_benign	0.151	benign	-0.135	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
S/N	0.1253	likely_benign	0.1256	benign	-0.336	Destabilizing	0.919	D	0.481	neutral	None	None	None	None	N
S/P	0.7504	likely_pathogenic	0.7661	pathogenic	-0.297	Destabilizing	0.995	D	0.641	neutral	D	0.554660909	None	None	N
S/Q	0.2633	likely_benign	0.2669	benign	-0.389	Destabilizing	0.507	D	0.411	neutral	None	None	None	None	N
S/R	0.262	likely_benign	0.2605	benign	-0.296	Destabilizing	0.976	D	0.599	neutral	None	None	None	None	N
S/T	0.0621	likely_benign	0.0629	benign	-0.39	Destabilizing	0.946	D	0.445	neutral	N	0.475494576	None	None	N
S/V	0.1392	likely_benign	0.1382	benign	-0.297	Destabilizing	0.988	D	0.617	neutral	None	None	None	None	N
S/W	0.2871	likely_benign	0.2844	benign	-0.974	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
S/Y	0.1478	likely_benign	0.141	benign	-0.664	Destabilizing	0.995	D	0.706	prob.neutral	N	0.475026902	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.