Submissions for variant NM_006019.4(TCIRG1):c.1209G>A (p.Met403Ile)

gnomAD frequency: 0.00095  dbSNP: rs140191063

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000345603	SCV000341073	uncertain significance	not provided	2016-04-15	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000778337	SCV000914534	uncertain significance	Autosomal recessive osteopetrosis 1	2018-11-15	criteria provided, single submitter	clinical testing	The TCIRG1 c.1209G>A (p.Met403Ile) missense variant has been reported in one study in which it was found in one individual with malignant infantile osteopetrosis, presumably in a compound heterozygous state with a nonsense variant (Steward et al. 2004). Control data are unavailable for this variant, which is reported at a frequency of 0.00151 in the European (non-Finnish) population of the Genome Aggregation Database. The evidence for this variant is limited. The p.Met403Ile variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for osteopetrosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae	RCV000345603	SCV003267091	likely benign	not provided	2024-01-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003930132	SCV004743709	likely benign	TCIRG1-related disorder	2023-03-09	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).