Submissions for variant NM_003000.3(SDHB):c.65G>C (p.Cys22Ser)

gnomAD frequency: 0.00057  dbSNP: rs141230910

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000206152	SCV000261872	likely benign	Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma	2025-02-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000573095	SCV000675060	likely benign	Hereditary cancer-predisposing syndrome	2018-08-24	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Eurofins Ntd Llc (ga)	RCV000596063	SCV000702012	uncertain significance	not provided	2016-10-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001095936	SCV001252116	benign	Carney-Stratakis syndrome	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV001101396	SCV001258000	benign	Hereditary pheochromocytoma-paraganglioma	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000596063	SCV001786016	uncertain significance	not provided	2024-09-16	criteria provided, single submitter	clinical testing	In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29386252, 26273102, 17376234, 25801821, 30171174)
Sema4, Sema4	RCV000573095	SCV002527086	likely benign	Hereditary cancer-predisposing syndrome	2021-09-02	criteria provided, single submitter	curation
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV005361203	SCV005912667	uncertain significance	Gastrointestinal stromal tumor; Cowden syndrome	2023-11-10	criteria provided, single submitter	clinical testing