TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4641	14146;14147;14148	chr2:178739312;178739311;178739310	chr2:179604039;179604038;179604037
N2AB	4324	13195;13196;13197	chr2:178739312;178739311;178739310	chr2:179604039;179604038;179604037
N2A	None	None	chr2:None	chr2:None
N2B	4278	13057;13058;13059	chr2:178739312;178739311;178739310	chr2:179604039;179604038;179604037
Novex-1	4403	13432;13433;13434	chr2:178739312;178739311;178739310	chr2:179604039;179604038;179604037
Novex-2	4470	13633;13634;13635	chr2:178739312;178739311;178739310	chr2:179604039;179604038;179604037
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-29
• Domain position: 36
• Structural Position: 52
• Q(SASA): 0.9343
• 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
N/D	None	None	None	N	0.077	0.11	None	gnomAD-4.0.0	1.59181E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85891E-06	0	0
N/I	rs1297520971	None	0.033	N	0.458	0.118	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/I	rs1297520971	None	0.033	N	0.458	0.118	None	gnomAD-4.0.0	6.57082E-06	None	None	None	None	N	None	2.41243E-05	0	None	0	0	None	0	0	0	0	0
N/S	None	None	None	N	0.066	0.113	None	gnomAD-4.0.0	1.59184E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43299E-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
N/A	0.1624	likely_benign	0.1752	benign	-0.103	Destabilizing	0.002	N	0.23	neutral	None	None	None	None	N
N/C	0.1951	likely_benign	0.2115	benign	0.164	Stabilizing	None	N	0.225	neutral	None	None	None	None	N
N/D	0.0853	likely_benign	0.0811	benign	0.329	Stabilizing	None	N	0.077	neutral	N	0.421438501	None	None	N
N/E	0.1776	likely_benign	0.1792	benign	0.29	Stabilizing	0.004	N	0.171	neutral	None	None	None	None	N
N/F	0.4799	ambiguous	0.5214	ambiguous	-0.664	Destabilizing	0.085	N	0.461	neutral	None	None	None	None	N
N/G	0.1022	likely_benign	0.1012	benign	-0.225	Destabilizing	None	N	0.077	neutral	None	None	None	None	N
N/H	0.1023	likely_benign	0.103	benign	-0.191	Destabilizing	0.196	N	0.317	neutral	N	0.447104771	None	None	N
N/I	0.2747	likely_benign	0.3255	benign	0.122	Stabilizing	0.033	N	0.458	neutral	N	0.442225615	None	None	N
N/K	0.1277	likely_benign	0.1287	benign	0.202	Stabilizing	None	N	0.073	neutral	N	0.425575998	None	None	N
N/L	0.2385	likely_benign	0.2802	benign	0.122	Stabilizing	0.009	N	0.283	neutral	None	None	None	None	N
N/M	0.2614	likely_benign	0.3036	benign	0.075	Stabilizing	0.497	N	0.342	neutral	None	None	None	None	N
N/P	0.6707	likely_pathogenic	0.7387	pathogenic	0.072	Stabilizing	0.018	N	0.323	neutral	None	None	None	None	N
N/Q	0.1783	likely_benign	0.1824	benign	-0.16	Destabilizing	0.009	N	0.27	neutral	None	None	None	None	N
N/R	0.1651	likely_benign	0.171	benign	0.25	Stabilizing	0.009	N	0.241	neutral	None	None	None	None	N
N/S	0.0685	likely_benign	0.0715	benign	-0.017	Destabilizing	None	N	0.066	neutral	N	0.413391973	None	None	N
N/T	0.114	likely_benign	0.1261	benign	0.075	Stabilizing	0.003	N	0.191	neutral	N	0.453344718	None	None	N
N/V	0.2727	likely_benign	0.3103	benign	0.072	Stabilizing	0.009	N	0.281	neutral	None	None	None	None	N
N/W	0.5631	ambiguous	0.6018	pathogenic	-0.782	Destabilizing	0.788	D	0.325	neutral	None	None	None	None	N
N/Y	0.1272	likely_benign	0.1355	benign	-0.443	Destabilizing	0.065	N	0.44	neutral	N	0.441485873	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.