Submissions for variant NM_004168.4(SDHA):c.1055G>A (p.Arg352Gln)

gnomAD frequency: 0.00009  dbSNP: rs199844384

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000411606	SCV000489339	uncertain significance	Paragangliomas 5	2016-09-20	criteria provided, single submitter	clinical testing
Invitae	RCV000463749	SCV000553876	uncertain significance	Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5	2024-01-27	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 352 of the SDHA protein (p.Arg352Gln). This variant is present in population databases (rs199844384, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. ClinVar contains an entry for this variant (Variation ID: 371975). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SDHA protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV000498298	SCV000590005	uncertain significance	not provided	2023-07-28	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Ambry Genetics	RCV000563279	SCV000674918	uncertain significance	Hereditary cancer-predisposing syndrome	2023-05-08	criteria provided, single submitter	clinical testing	The p.R352Q variant (also known as c.1055G>A), located in coding exon 8 of the SDHA gene, results from a G to A substitution at nucleotide position 1055. The arginine at codon 352 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV000765832	SCV000897227	uncertain significance	Leigh syndrome; Mitochondrial complex II deficiency, nuclear type 1; Dilated cardiomyopathy 1GG; Paragangliomas 5	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001153526	SCV001314821	benign	Hereditary pheochromocytoma-paraganglioma	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001153527	SCV001314822	uncertain significance	Leigh syndrome	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001153528	SCV001314823	uncertain significance	Mitochondrial complex II deficiency, nuclear type 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Sema4, Sema4	RCV000563279	SCV002527691	likely benign	Hereditary cancer-predisposing syndrome	2021-06-30	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000411606	SCV004018613	uncertain significance	Paragangliomas 5	2023-04-21	criteria provided, single submitter	clinical testing	This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics	RCV003475997	SCV004202388	uncertain significance	Dilated cardiomyopathy 1GG	2024-03-25	criteria provided, single submitter	clinical testing
University of Washington Department of Laboratory Medicine, University of Washington	RCV000411606	SCV001446376	likely benign	Paragangliomas 5	2019-03-01	no assertion criteria provided	research
GenomeConnect - Invitae Patient Insights Network	RCV003483608	SCV004228595	not provided	Mitochondrial complex II deficiency, nuclear type 1; Dilated cardiomyopathy 1GG; Paragangliomas 5		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 08-02-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.